1 3690 164 INFLAMMATORY BOWEL DISEASE: GENETICS, EPIGENETICS, AND PATHOGENESIS. INFLAMMATORY BOWEL DISEASES (IBDS) ARE COMPLEX, MULTIFACTORIAL DISORDERS CHARACTERIZED BY CHRONIC RELAPSING INTESTINAL INFLAMMATION. ALTHOUGH ETIOLOGY REMAINS LARGELY UNKNOWN, RECENT RESEARCH HAS SUGGESTED THAT GENETIC FACTORS, ENVIRONMENT, MICROBIOTA, AND IMMUNE RESPONSE ARE INVOLVED IN THE PATHOGENESIS. EPIDEMIOLOGICAL EVIDENCE FOR A GENETIC CONTRIBUTION IS DEFINED: 15% OF PATIENTS WITH CROHN'S DISEASE (CD) HAVE AN AFFECTED FAMILY MEMBER WITH IBD, AND TWIN STUDIES FOR CD HAVE SHOWN 50% CONCORDANCE IN MONOZYGOTIC TWINS COMPARED TO <10% IN DIZYGOTICS. THE MOST RECENT AND LARGEST GENETIC ASSOCIATION STUDIES, WHICH EMPLOYED GENOME-WIDE ASSOCIATION DATA FOR OVER 75,000 PATIENTS AND CONTROLS, IDENTIFIED 163 SUSCEPTIBILITY LOCI FOR IBD. MORE RECENTLY, A TRANS-ETHNIC ANALYSIS, INCLUDING OVER 20,000 INDIVIDUALS, IDENTIFIED AN ADDITIONAL 38 NEW IBD LOCI. ALTHOUGH MOST CASES ARE CORRELATED WITH POLYGENIC CONTRIBUTION TOWARD GENETIC SUSCEPTIBILITY, THERE IS A SPECTRUM OF RARE GENETIC DISORDERS THAT CAN CONTRIBUTE TO EARLY-ONSET IBD (BEFORE 5 YEARS) OR VERY EARLY ONSET IBD (BEFORE 2 YEARS). GENETIC VARIANTS THAT CAUSE THESE DISORDERS HAVE A WIDE EFFECT ON GENE FUNCTION. THESE VARIANTS ARE SO RARE IN ALLELE FREQUENCY THAT THE GENETIC SIGNALS ARE NOT DETECTED IN GENOME-WIDE ASSOCIATION STUDIES OF PATIENTS WITH IBD. WITH RECENT ADVANCES IN SEQUENCING TECHNIQUES, ~50 GENETIC DISORDERS HAVE BEEN IDENTIFIED AND ASSOCIATED WITH IBD-LIKE IMMUNOPATHOLOGY. MONOGENIC DEFECTS HAVE BEEN FOUND TO ALTER INTESTINAL IMMUNE HOMEOSTASIS THROUGH MANY MECHANISMS. CANDIDATE GENE RESEQUENCING SHOULD BE CARRIED OUT IN EARLY-ONSET PATIENTS IN CLINICAL PRACTICE. THE EVIDENCE THAT GENETIC FACTORS CONTRIBUTE IN SMALL PART TO DISEASE PATHOGENESIS CONFIRMS THE IMPORTANT ROLE OF MICROBIAL AND ENVIRONMENTAL FACTORS. EPIGENETIC FACTORS CAN MEDIATE INTERACTIONS BETWEEN ENVIRONMENT AND GENOME. EPIGENETIC MECHANISMS COULD AFFECT DEVELOPMENT AND PROGRESSION OF IBD. EPIGENOMICS IS AN EMERGING FIELD, AND FUTURE STUDIES COULD PROVIDE NEW INSIGHT INTO THE PATHOGENESIS OF IBD.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
2 3029  37 GENETICS OF INFLAMMATORY BOWEL DISEASES: A COMPARISON BETWEEN WESTERN AND EASTERN PERSPECTIVES. INFLAMMATORY BOWEL DISEASE (IBD) IS A CHRONIC RELAPSING INTESTINAL INFLAMMATORY DISORDER WITH UNIDENTIFIED CAUSES. CURRENTLY, STUDIES INDICATE THAT IBD RESULTS FROM A COMPLEX INTERPLAY BETWEEN VARIOUS GENETIC AND ENVIRONMENTAL FACTORS THAT PRODUCE INTESTINAL INFLAMMATION. HOWEVER, THESE FACTORS MAY DIFFER FOR ASIANS AND CAUCASIANS. THUS, DIFFERENCES IN EPIDEMIOLOGY, GENETIC VARIANTS, AND CLINICAL PHENOTYPES OF IBD HAVE BEEN OBSERVED BETWEEN THE TWO POPULATIONS. UNDERSTANDING THE DISCREPANCIES BETWEEN DATA FROM POPULATIONS WITH DIFFERENT GENETIC BACKGROUNDS AND ENVIRONMENTAL FACTORS MAY REVEAL FUNDAMENTAL ASPECTS OF IBD PATHOGENESIS. ACCORDINGLY, THIS REVIEW WILL SUMMARIZE THE CURRENT KNOWLEDGE OF IBD GENETICS STUDIED IN ASIAN COUNTRIES AND COMPARE IT WITH THAT FROM WESTERN COUNTRIES, WITH SPECIAL FOCUS ON INNATE BACTERIAL SENSING, AUTOPHAGY, AND THE INTERLEUKIN-23 RECEPTOR-T HELPER CELL 17 PATHWAY. THE EPIGENETIC NATURE OF IBD PATHOGENESIS AS WELL AS THE PHARMACOGENETICS RELATED TO THE USE OF IMMUNOMODULATORS WILL ALSO BE BRIEFLY COVERED.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
3 3016  46 GENETICS AND EPIGENETICS OF IBD. INFLAMMATORY BOWEL DISEASES (IBD) ARE CHRONIC INTERMITTENT INFLAMMATORY DISORDERS OF THE GASTROINTESTINAL TRACT OF UNKNOWN ETIOLOGY BUT A CLEAR GENETIC PREDISPOSITION. PROMPTED BY THE FIRST INVESTIGATIONS ON IBD FAMILIES AND TWINS, THE GENETIC AND EPIGENETIC STUDIES HAVE PRODUCED AN UNPRECEDENTED AMOUNT OF INFORMATION IN COMPARISON WITH OTHER IMMUNE-MEDIATED OR COMPLEX DISEASES. NEW INFLAMMATORY PATHWAYS AND POSSIBLE MECHANISMS OF ACTION HAVE BEEN DISCLOSED, POTENTIALLY LEADING TO NEW-TARGETED THERAPY. HOWEVER, THE IDENTIFICATION OF GENETIC MARKERS DUE TO THE GREAT DISEASE HETEROGENEITY AND THE OVERWHELMING CONTRIBUTION OF ENVIRONMENTAL RISK FACTORS HAS NOT MODIFIED YET THE DISEASE MANAGEMENT. THE POSSIBILITY FOR THE FUTURE OF A BETTER PREDICTION OF DISEASE COURSE, RESPONSE TO THERAPY AND THERAPY-RELATED ADVERSE EVENTS MAY ALLOW A MORE EFFICIENT AND PERSONALIZED STRATEGY. THIS REVIEW WILL FOCUS ON MORE RECENT DISCOVERIES THAT MAY POTENTIALLY BE OF RELEVANCE IN DAILY CLINICAL PRACTICE.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
4 3541  46 IMMUNOEPIGENETIC REGULATION OF INFLAMMATORY BOWEL DISEASE: CURRENT INSIGHTS INTO NOVEL EPIGENETIC MODULATIONS OF THE SYSTEMIC IMMUNE RESPONSE. THE IMMUNE SYSTEM AND ENVIRONMENTAL FACTORS ARE INVOLVED IN VARIOUS DISEASES, SUCH AS INFLAMMATORY BOWEL DISEASE (IBD), THROUGH THEIR EFFECT ON GENETICS, WHICH MODULATES IMMUNE CELLS. IBD ENCOMPASSES TWO MAIN PHENOTYPES, CROHN'S DISEASE, AND ULCERATIVE COLITIS, WHICH ARE MANIFESTED AS CHRONIC AND SYSTEMIC RELAPSE-REMITTING GASTROINTESTINAL TRACT DISORDERS WITH RISING GLOBAL INCIDENCE AND PREVALENCE. THE PATHOPHYSIOLOGY OF IBD IS COMPLEX AND NOT FULLY UNDERSTOOD. EPIGENETIC RESEARCH HAS RESULTED IN VALUABLE INFORMATION FOR UNRAVELING THE ETIOLOGY OF THIS IMMUNE-MEDIATED DISEASE. THUS, THE MAIN OBJECTIVE OF THE PRESENT REVIEW IS TO SUMMARIZE THE CURRENT FINDINGS ON THE ROLE OF EPIGENETIC MECHANISMS IN IBD TO SHED LIGHT ON THEIR POTENTIAL CLINICAL RELEVANCE. THIS REVIEW FOCUSES ON THE LATEST EVIDENCE REGARDING PERIPHERAL BLOOD MONONUCLEAR CELLS AND EPIGENETIC CHANGES IN HISTONE MODIFICATION, DNA METHYLATION, AND TELOMERE SHORTENING IN IBD. THE VARIOUS IDENTIFIED EPIGENETIC DNA PROFILES WITH CLINICAL VALUE IN IBD COULD BE USED AS BIOMARKERS FOR MORE ACCURATELY PREDICTING DISEASE DEVELOPMENT, TREATMENT RESPONSE, AND THERAPY-RELATED ADVERSE EVENTS. ULTIMATELY, THE INFORMATION PRESENTED HERE COULD BE OF POTENTIAL RELEVANCE FOR FUTURE CLINICAL PRACTICE IN DEVELOPING MORE EFFICIENT AND PRECISE MEDICINE TO IMPROVE THE QUALITY OF LIFE FOR PATIENTS WITH IBD.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
5 6821  46 [GASTROINTESTINAL MANIFESTATIONS IN IMMUNODEFICIENCIES WITH MONOGENIC ORIGIN]. ALTHOUGH VERY EARLY ONSET INFLAMMATORY BOWEL DISEASE THAT DEVELOPS IN EARLY CHILDHOOD (BEFORE THE AGE OF 6 YEARS) HAS A DIFFERENT ETIOLOGY FROM CROHN'S DISEASE AND ULCERATIVE COLITIS, IT IS ALSO CHARACTERIZED BY CHRONIC INFLAMMATION OF THE GASTROINTESTINAL TRACT. BASICALLY, VERY EARLY ONSET INFLAMMATORY BOWEL DISEASE SHOULD BE CONSIDERED AS AN IMMUNODEFICIENCY WITH MONOGENIC ORIGIN WHERE BOTH GASTROINTESTINAL MANIFESTATIONS AND SYMPTOMS OF IMMUNODEFICIENCIES MAY DEVELOP IN VARIABLE COMBINATIONS. HOWEVER, IN THE FUTURE, THE EVALUATION OF GENETIC ALTERATIONS IN THE BACKGROUND OF THE DISEASE WILL PROBABLY BE PERFORMED BY NEXT-GENERATION SEQUENCING TECHNOLOGY; ONE SHOULD ALSO CONSIDER THAT THE SEQUENCE OF THE DNA STANDS IN CONTINUOUS INTERACTION WITH A WIDE VARIETY OF ENVIRONMENTAL EFFECTS, AMONG WHICH NUTRITION SHOULD BE EMPHASIZED BY ALL MEANS. EPIGENETIC ALTERATIONS THAT ARE INDUCED BY ENVIRONMENTAL FACTORS, COULD CONTRIBUTE TO THE PATHOGENESIS OF INFLAMMATORY BOWEL DISEASES THAT DEVELOP DURING CHILDHOOD, THEREFORE, THEY SHOULD ALSO BE IDENTIFIED DURING FURTHER RESEARCH. IT HAS A KEY SIGNIFICANCE TO ESTABLISH THE DIAGNOSIS OF VERY EARLY ONSET INFLAMMATORY BOWEL DISEASE AS EARLY AS POSSIBLE, BECAUSE THIS COULD GIVE THE OPPORTUNITY TO START THE ADEQUATE TREATMENT WHICH IS BONE MARROW TRANSPLANTATION IN THE CASE OF MONOGENIC IMMUNODEFICIENCIES. ORV HETIL. 2018; 159(49): 2050-2056.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
6 2945  32 GENETIC AND EPIGENETIC BASIS OF PSORIASIS PATHOGENESIS. PSORIASIS IS A CHRONIC INFLAMMATORY SKIN DISEASE WHOSE PREVALENCE VARIES AMONG DIFFERENT POPULATIONS WORLDWIDE. IT IS A COMPLEX MULTI-FACTORIAL DISEASE AND THE EXACT ETIOLOGY IS LARGELY UNKNOWN. FAMILY BASED STUDIES HAVE INDICATED A GENETIC PREDISPOSITION; HOWEVER THEY CANNOT FULLY EXPLAIN THE DISEASE PATHOGENESIS. IN ADDITION TO GENETIC SUSCEPTIBILITY, ENVIRONMENTAL AS WELL AS GENDER AND AGE RELATED FACTORS WERE ALSO BEEN FOUND TO BE ASSOCIATED. RECENTLY, IMBALANCES IN EPIGENETIC NETWORKS ARE INDICATED TO BE CAUSATIVE ELEMENTS IN PSORIASIS. THE PRESENT KNOWLEDGE OF EPIGENETIC INVOLVEMENT, MAINLY THE DNA METHYLATION, CHROMATIN MODIFICATIONS AND MIRNA DEREGULATION IS SURVEYED HERE. AN INTEGRATED APPROACH CONSIDERING GENETIC AND EPIGENETIC ANOMALIES IN THE LIGHT OF IMMUNOLOGICAL NETWORK MAY EXPLORE THE PATHOGENESIS OF PSORIASIS.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
7 3017  40 GENETICS AND EPIGENETICS OF INFLAMMATORY BOWEL DISEASE. THE RELEVANCE OF GENETIC AND EPIGENETIC ALTERATIONS IN THE PATHOGENESIS OF INFLAMMATORY BOWEL DISEASE (IBD) IS STILL POORLY UNDERSTOOD. SO FAR, 240 RISK GENE LOCI HAVE BEEN ASSOCIATED WITH IBD. THEY ARE MAINLY INVOLVED IN REGULATING INNATE AND ADAPTIVE IMMUNITY, AS WELL AS MAINTAINING INTESTINAL EPITHELIAL BARRIER FUNCTION. HOWEVER, THE FUNCTIONAL CONSEQUENCES OF THE IDENTIFIED GENETIC POLYMORPHISMS FOR IBD PATHOGENESIS IN VIVO ARE OFTEN UNKNOWN. EVEN LESS IS KNOWN ABOUT THE ROLE FOR EPIGENETIC MODIFICATIONS IN IBD PATHOGENESIS. THOUGH A NUMBER OF EPIGENETIC EVENTS SEEM TO BE CAUSATIVELY INVOLVED IBD PATHOGENESIS, OUR KNOWLEDGE ABOUT THE FUNCTIONAL RELEVANCE OF THOSE EPIGENETIC MODIFICATIONS IS SCANTY. THIS OPENS UP A BROAD RESEARCH FIELD THAT GENERATES NOVEL INSIGHTS INTO THE PATHOPHYSIOLOGY OF INTESTINAL AND CHRONIC INFLAMMATORY DISEASE. PATTERNS OF DNA METHYLATION AND HISTONE MODIFICATIONS MIGHT SERVE NOT ONLY AS BIOMARKERS OF DISEASE ACTIVITY OR DISEASE COURSE, BUT ALSO AS NEW TARGETS IN THERAPEUTIC INTERVENTIONS IN IBD PATIENTS.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
8 1137  44 COMPREHENSIVE PHENOTYPING IN INFLAMMATORY BOWEL DISEASE: SEARCH FOR BIOMARKER ALGORITHMS IN THE TRANSKINGDOM INTERACTIONS CONTEXT. INFLAMMATORY BOWEL DISEASE (IBD) IS THE MOST COMMON FORM OF INTESTINAL INFLAMMATION ASSOCIATED WITH A DYSREGULATED IMMUNE SYSTEM RESPONSE TO THE COMMENSAL MICROBIOTA IN A GENETICALLY SUSCEPTIBLE HOST. IBD INCLUDES ULCERATIVE COLITIS (UC) AND CROHN'S DISEASE (CD), BOTH OF WHICH ARE REMARKABLY HETEROGENEOUS IN THEIR CLINICAL PRESENTATION AND RESPONSE TO TREATMENT. THIS TRANSLATES INTO A NOTABLE DIAGNOSTIC CHALLENGE, ESPECIALLY IN UNDERDEVELOPED COUNTRIES WHERE IBD IS ON THE RISE AND ACCESS TO DIAGNOSIS OR TREATMENT IS NOT ALWAYS ACCESSIBLE FOR CHRONIC DISEASES. THE PRESENT WORK CHARACTERIZED, FOR THE FIRST TIME IN OUR REGION, EPIGENETIC BIOMARKERS AND GUT MICROBIAL PROFILES ASSOCIATED WITH UC AND CD PATIENTS IN THE BUENOS AIRES METROPOLITAN AREA AND REVEALED DIFFERENCES BETWEEN NON-IBD CONTROLS AND IBD PATIENTS. GENERAL METABOLIC FUNCTIONS ASSOCIATED WITH THE GUT MICROBIOTA, AS WELL AS CORE MICROORGANISMS WITHIN GROUPS, WERE ALSO ANALYZED. ADDITIONALLY, THE GUT MICROBIOTA ANALYSIS WAS INTEGRATED WITH RELEVANT CLINICAL, BIOCHEMICAL AND EPIGENETIC MARKERS CONSIDERED IN THE FOLLOW-UP OF PATIENTS WITH IBD, WITH THE AIM OF GENERATING MORE POWERFUL DIAGNOSTIC TOOLS TO DISCRIMINATE PHENOTYPES. OVERALL, OUR STUDY PROVIDES NEW INSIGHTS INTO DATA ANALYSIS ALGORITHMS TO PROMOTE COMPREHENSIVE PHENOTYPING TOOLS USING QUANTITATIVE AND QUALITATIVE ANALYSIS IN A TRANSKINGDOM INTERACTIONS NETWORK CONTEXT.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
9 2027  47 EPIGENETIC CHANGES IN CHRONIC INFLAMMATORY DISEASES. THE NUMBER OF PEOPLE DIAGNOSED WITH CHRONIC INFLAMMATORY DISEASES HAS INCREASED NOTEWORTHY IN THE LAST 40 YEARS. SPONDYLOARTHRITIS (SPA), INFLAMMATORY BOWEL DISEASES (IBD), AND PSORIASIS ARE THE MOST FREQUENT CHRONIC INFLAMMATORY DISEASES, RESULTING FROM A COMBINATION OF GENETIC PREDISPOSITION AND ENVIRONMENTAL FACTORS. EPIGENETIC MODIFICATIONS INCLUDE DNA METHYLATION, HISTONE MODIFICATIONS, AND SMALL AND LONG NONCODING RNAS. THEY ARE INFLUENCED BY ENVIRONMENTAL EXPOSURE, LIFE-STYLE, AND AGING AND HAVE RECENTLY BEEN SHOWN TO BE ALTERED IN MANY COMPLEX DISEASES INCLUDING INFLAMMATORY DISEASES. WHILE EPIGENETIC MODIFICATIONS HAVE BEEN WELL CHARACTERIZED IN OTHER DISEASES SUCH AS CANCER AND AUTOIMMUNE DISEASES, KNOWLEDGE ON CHANGES IN INFLAMMATORY DISEASES IS LAGGING BEHIND WITH SOME DISEASE-SPECIFIC DIFFERENCES. WHILE THE DNA METHYLATION PROFILE OF DIFFERENT CELL TYPES IN PATIENTS WITH IBD HAS BEEN RELATIVELY WELL DESCRIBED, LESS IS KNOWN ON CHANGES IMPLICATED IN PSORIASIS, AND NO SYSTEMATIC GENOME-WIDE STUDIES HAVE SO FAR BEEN PERFORMED IN SPA. IN THIS CHAPTER, WE REVIEW IN DETAIL THE REPORTED CHANGES IN PATTERNS OF DNA METHYLATION AND POSTTRANSLATIONAL HISTONE MODIFICATIONS IN CHRONIC INFLAMMATORY DISEASES HIGHLIGHTING POTENTIAL CONNECTIONS BETWEEN DISEASE-ASSOCIATED PATHOPHYSIOLOGICAL CHANGES SUCH AS THE DYSBIOSIS OF THE MICROBIOME OR GENETIC VARIATIONS ASSOCIATED WITH DISEASE SUSCEPTIBILITY AND THE EPIGENOME. WE ALSO DISCUSS IMPORTANT PARAMETERS OF MEANINGFUL EPIGENETIC STUDIES SUCH AS THE USE OF WELL DEFINED, DISEASE-RELEVANT CELL POPULATIONS, AND ELUDE ON THE POTENTIAL FUTURE OF ENGINEERING OF THE EPIGENOME IN INFLAMMATORY DISEASES.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
10 1522  50 DNA METHYLATION CHANGE PROFILING OF COLORECTAL DISEASE: SCREENING TOWARDS CLINICAL USE. COLON CANCER REMAINS ONE OF THE LEADING CAUSES OF CANCER-RELATED DEATHS WORLDWIDE. TRANSFORMATION OF COLON EPITHELIAL CELLS INTO INVASIVE ADENOCARCINOMAS HAS BEEN WELL KNOWN TO BE DUE TO THE ACCUMULATION OF MULTIPLE GENETIC AND EPIGENETIC CHANGES. IN THE PAST DECADE, THE ETIOLOGY OF INFLAMMATORY BOWEL DISEASE (IBD) WHICH IS CHARACTERIZED BY CHRONIC INFLAMMATION OF THE INTESTINAL MUCOSA, WAS ONLY PARTIALLY EXPLAINED BY GENETIC STUDIES PROVIDING SUSCEPTIBILITY LOCI, BUT RECENTLY EPIGENETIC STUDIES HAVE PROVIDED CRITICAL EVIDENCES AFFECTING IBD PATHOGENESIS. OVER THE PAST DECADE, A DEEP UNDERSTANDING OF EPIGENETICS ALONG WITH TECHNOLOGICAL ADVANCES HAVE LED TO IDENTIFYING NUMEROUS GENES THAT ARE REGULATED BY PROMOTER DNA HYPERMETHYLATION IN COLORECTAL DISEASES. RECENT ADVANCES IN OUR UNDERSTANDING OF THE ROLE OF DNA METHYLATION IN COLORECTAL DISEASES COULD IMPROVE A MULTITUDE OF POWERFUL DNA METHYLATION-BASED BIOMARKERS, PARTICULARLY FOR USE AS DIAGNOSIS, PROGNOSIS, AND PREDICTION FOR THERAPEUTIC APPROACHES. THIS REVIEW FOCUSES ON THE EMERGING POTENTIAL FOR TRANSLATIONAL RESEARCH OF EPIGENETIC ALTERATIONS INTO CLINICAL UTILITY AS MOLECULAR BIOMARKERS. MOREOVER, THIS REVIEW DISCUSSES RECENT PROGRESS REGARDING THE IDENTIFICATION OF UNKNOWN HYPERMETHYLATED GENES IN COLON CANCERS AND IBD, AS WELL AS THEIR POSSIBLE ROLE IN CLINICAL PRACTICE, WHICH WILL HAVE IMPORTANT CLINICAL SIGNIFICANCE, PARTICULARLY IN THE ERA OF THE PERSONALIZED MEDICINE.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
11 3681  46 INFLAMMATION, DNA METHYLATION AND COLITIS-ASSOCIATED CANCER. INFLAMMATION CAN RESULT FROM A RANGE OF SOURCES INCLUDING MICROBIAL INFECTIONS, EXPOSURE TO ALLERGENS AND TOXIC CHEMICALS, AUTOIMMUNE DISEASE AND OBESITY. A WELL-BALANCED IMMUNE RESPONSE CAN BE ANTI-TUMORIGENIC; HOWEVER, A SUSTAINED OR CHRONIC INFLAMMATORY RESPONSE IS GENERALLY HARMFUL AS THE IMMUNE RESPONSE BECOMES DISTORTED. A CAUSAL LINK BETWEEN CHRONIC INFLAMMATION AND CANCER IS NOW WELL ACCEPTED AND MANY CHRONICALLY INFLAMED ORGANS OF THE GASTROINTESTINAL TRACT SHOW THIS ASSOCIATION. FOR EXAMPLE, PATIENTS WITH INFLAMMATORY BOWEL DISEASE (IBD), INCLUDING BOTH ULCERATIVE COLITIS AND CROHN'S DISEASE, HAVE A 2- TO 3-FOLD GREATER LIFETIME RISK OF DEVELOPING COLORECTAL CANCER COMPARED WITH THE GENERAL POPULATION. THE DEVELOPMENT OF COLITIS-ASSOCIATED CANCER (CAC) IS THOUGHT TO BE MULTIFACETED AND IS PROBABLY DUE TO A COMBINATION OF GENETIC FACTORS, EPIGENETIC FACTORS AND THE DURATION, EXTENT AND SEVERITY OF DISEASE. RECENTLY, EPIGENETIC ALTERATIONS, IN PARTICULAR ALTERATIONS IN DNA METHYLATION, HAVE BEEN OBSERVED DURING INFLAMMATION AND INFLAMMATION-ASSOCIATED CARCINOGENESIS. THE MEDIATORS OF THIS, THE SIGNIFICANCE OF THESE CHANGES IN DNA METHYLATION AND THE EFFECT THIS HAS ON GENE EXPRESSION AND THE MALIGNANT TRANSFORMATION OF THE EPITHELIAL CELLS DURING IBD AND CAC ARE DISCUSSED IN THIS REVIEW. THE RECENT ADVANCES IN TECHNOLOGIES TO STUDY GENOME-WIDE DNA METHYLATION AND THE THERAPEUTIC POTENTIAL OF UNDERSTANDING THESE MOLECULAR MECHANISMS ARE ALSO HIGHLIGHTED.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
12  738  35 CANCER SUSCEPTIBILITY: EPIGENETIC MANIFESTATION OF ENVIRONMENTAL EXPOSURES. CANCER IS A DISEASE THAT RESULTS FROM BOTH GENETIC AND EPIGENETIC CHANGES. DISCORDANT PHENOTYPES AND VARYING INCIDENCES OF COMPLEX DISEASES SUCH AS CANCER IN MONOZYGOTIC TWINS AS WELL AS GENETICALLY IDENTICAL LABORATORY ANIMALS HAVE LONG BEEN ATTRIBUTED TO DIFFERENCES IN ENVIRONMENTAL EXPOSURES. ACCUMULATING EVIDENCE INDICATES, HOWEVER, THAT DISPARITIES IN GENE EXPRESSION RESULTING FROM VARIABLE MODIFICATIONS IN DNA METHYLATION AND CHROMATIN STRUCTURE IN RESPONSE TO THE ENVIRONMENT ALSO PLAY A ROLE IN DIFFERENTIAL SUSCEPTIBILITY TO DISEASE. DESPITE A GROWING CONSENSUS ON THE IMPORTANCE OF EPIGENETICS IN THE ETIOLOGY OF CHRONIC HUMAN DISEASES, THE GENES MOST PRONE TO EPIGENETIC DYSREGULATION ARE INCOMPLETELY DEFINED. MOREOVER, NEITHER THE ENVIRONMENTAL AGENTS MOST STRONGLY AFFECTING THE EPIGENOME NOR THE CRITICAL WINDOWS OF VULNERABILITY TO ENVIRONMENTALLY INDUCED EPIGENETIC ALTERATIONS ARE ADEQUATELY CHARACTERIZED. THESE MAJOR DEFICITS IN KNOWLEDGE MARKEDLY IMPAIR OUR ABILITY TO UNDERSTAND FULLY THE ETIOLOGY OF CANCER AND THE IMPORTANCE OF THE EPIGENOME IN DIAGNOSING AND PREVENTING THIS DEVASTATING DISEASE.	2007	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
13 4283  34 MICRORNA BIOMARKERS IN IBD-DIFFERENTIAL DIAGNOSIS AND PREDICTION OF COLITIS-ASSOCIATED CANCER. INFLAMMATORY BOWEL DISEASE (IBD) INCLUDES CROHN'S DISEASE (CD) AND ULCERATIVE COLITIS (UC). THESE ARE CHRONIC AUTOIMMUNE DISEASES OF UNKNOWN ETIOLOGY AFFECTING THE GASTROINTESTINAL TRACT. THE IBD POPULATION INCLUDES A HETEROGENEOUS GROUP OF PATIENTS WITH VARYING DISEASE COURSES REQUIRING PERSONALIZED TREATMENT PROTOCOLS. THE COMPLEXITY OF THE DISEASE OFTEN DELAYS THE DIAGNOSIS AND THE INITIATION OF APPROPRIATE TREATMENTS. IN A SUBSET OF PATIENTS, IBD LEADS TO COLITIS-ASSOCIATED CANCER (CAC). MICRORNAS ARE SINGLE-STRANDED REGULATORY NONCODING RNAS OF 18 TO 22 NUCLEOTIDES WITH PUTATIVE ROLES IN THE PATHOGENESIS OF IBD AND COLORECTAL CANCER. THEY HAVE BEEN EXPLORED AS BIOMARKERS AND THERAPEUTIC TARGETS. BOTH TISSUE-DERIVED AND CIRCULATING MICRORNAS HAVE EMERGED AS PROMISING BIOMARKERS IN THE DIFFERENTIAL DIAGNOSIS AND IN THE PROGNOSIS OF DISEASE SEVERITY OF IBD AS WELL AS PREDICTIVE BIOMARKERS IN DRUG RESISTANCE. IN ADDITION, KNOWLEDGE OF THE CELLULAR LOCALIZATION OF DIFFERENTIALLY EXPRESSED MICRORNAS IS A PREREQUISITE FOR DECIPHERING THE BIOLOGICAL ROLE OF THESE IMPORTANT EPIGENETIC REGULATORS AND THE CELLULAR LOCALIZATION MAY EVEN CONTRIBUTE TO AN ALTERNATIVE REPERTOIRE OF BIOMARKERS. IN THIS REVIEW, WE DISCUSS FINDINGS BASED ON RT-QPCR, MICROARRAY PROFILING, NEXT GENERATION SEQUENCING AND IN SITU HYBRIDIZATION OF MICRORNA BIOMARKERS IDENTIFIED IN THE CIRCULATION AND IN TISSUE BIOPSIES.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
14 3706  47 INFLUENCE OF GENETICS ON DISEASE SUSCEPTIBILITY AND PROGRESSION. FOR MANY CHRONIC DISEASES, THE INFLUENCE OF GENETICS IS COMPLEX AND PHENOTYPES DO NOT CONFORM TO SIMPLE MENDELIAN PATTERNS OF INHERITANCE. DISCUSSED HERE ARE TWO TYPES OF GENETIC INFLUENCES ON HEALTHY AGING. THE FIRST INVOLVES VARIATION IN THE GENE SEQUENCE ITSELF AND HOW THIS MAY INFLUENCE DISEASE SUSCEPTIBILITY, PROGRESSION, AND SEVERITY, INTERACTING WITH OTHER RECOGNIZED RISK FACTORS. THE SECOND INVOLVES EPIGENETIC REGULATORY MECHANISMS THAT MAY POTENTIALLY PROVIDE INSIGHT INTO HOW ENVIRONMENTAL INFLUENCES AFFECT THE EXPRESSED GENOME, THUS IMPROVING OUR UNDERSTANDING OF THE GENETIC MECHANISMS UNDERLYING MULTIFACTORIAL DISEASES. THE INTERLEUKIN-1 FAMILY OF CYTOKINES CAN BE USED TO ILLUSTRATE HOW GENETIC SEQUENCE VARIATION MAY AFFECT SUCH DISEASES. THIS CYTOKINE FAMILY PLAYS A KEY ROLE IN MEDIATING INFLAMMATION, WHICH IS NOW UNDERSTOOD TO BE A CENTRAL COMPONENT OF A GROWING NUMBER OF CHRONIC DISEASES. RECENT WORK HAS REVEALED MANY SEQUENCE VARIATIONS IN THE REGULATORY DNA OF GENES ENCODING IMPORTANT MEMBERS OF THE INTERLEUKIN-1 FAMILY, AND THESE VARIATIONS ARE ASSOCIATED WITH DIFFERENTIAL EFFECTS ON THE INFLAMMATORY RESPONSE. THE INTERACTIONS OF ENVIRONMENTAL FACTORS WITH BOTH DNA SEQUENCE VARIATIONS AND EPIGENETIC MODIFICATIONS ARE LIKELY TO DETERMINE THE PHENOTYPES OF MULTIFACTORIAL DISEASES OF AGING AS WELL AS THE PHENOTYPE OF HEALTHY AGING.	2007	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
15 4692  63 NEWS FROM THE "5TH INTERNATIONAL MEETING ON INFLAMMATORY BOWEL DISEASES" CAPRI 2010. AT THE "5TH INTERNATIONAL MEETING ON INFLAMMATORY BOWEL DISEASES SELECTED TOPICS OF INFLAMMATORY BOWEL DISEASE (IBD), INCLUDING THE ENVIRONMENT, GENETICS, THE GUT FLORA, THE CELL RESPONSE AND IMMUNOMODULATION WERE DISCUSSED IN ORDER TO BETTER UNDERSTAND SPECIFIC CLINICAL AND THERAPEUTIC ASPECTS. THE INCIDENCE OF IBD CONTINUES TO RISE, BOTH IN LOW AND IN HIGH-INCIDENCE AREAS. IT IS BELIEVED THAT FACTORS ASSOCIATED WITH 'WESTERNIZATION' MAY BE CONDITIONING THE EXPRESSION OF THESE DISORDERS. THE INCREASED INCIDENCE OF IBD AMONG MIGRANTS FROM LOW-INCIDENCE TO HIGH-INCIDENCE AREAS WITHIN THE SAME GENERATION SUGGESTS A STRONG ENVIRONMENTAL INFLUENCE. THE DEVELOPMENT OF GENOME-WIDE ASSOCIATION SCANNING (GWAS) TECHNOLOGIES HAS LEAD TO THE DISCOVERY OF MORE THAN 100 IBD LOCI. SOME, AS THE TH 17 PATHWAY GENES, ARE SHARED BETWEEN CROHN'S DISEASE (CD) AND ULCERATIVE COLITIS (UC), WHILE OTHER ARE IBD SUBTYPE-SPECIFIC (AUTOPHAGY GENES, EPITHELIAL BARRIER GENES). DISEASE-SPECIFIC THERAPIES TARGETING THESE PATHWAYS SHOULD BE DEVELOPED. EPIGENETIC REGULATION OF THE INFLAMMATORY RESPONSE ALSO APPEARS TO PLAY AN IMPORTANT ROLE IN THE PATHOGENESIS OF IBD. THE IMPORTANCE OF GUT FLORA IN INTESTINAL HOMEOSTASIS AND INFLAMMATION WAS REINFORCED, THE CONCEPTS OF EUBIOSIS AND DYSBIOSIS WERE INTRODUCED, AND SOME STRATEGIES FOR REVERTING DYSBIOSIS TO A HOMEOSTATIC STATE OF EUBIOSIS WERE PROPOSED. THE CURRENT STATUS OF STUDIES ON THE HUMAN GUT MICROBIOTA METAGENOME, METAPROTOME, AND METABOLOME WAS ALSO PRESENTED. THE CELL RESPONSE IN INFLAMMATION, INCLUDING ENDOPLASMIC RETICULUM (ER) STRESS RESPONSES, AUTOPHAGY AND INFLAMMASOME-DEPENDENT EVENTS WERE RELATED TO IBD PATHOGENESIS. IT WAS SUGGESTED THAT INFLAMMATION-ASSOCIATED ER STRESS RESPONSES MAY BE A COMMON TRAIT IN THE PATHOGENESIS OF VARIOUS CHRONIC IMMUNE AND METABOLIC DISEASES. HOW INNATE AND ADAPTIVE IMMUNITY SIGNALING EVENTS CAN PERPETUATE CHRONIC INFLAMMATION WAS DISCUSSED EXTENSIVELY. SIGNAL TRANSDUCTION PATHWAYS PROVIDE INTRACELLULAR MECHANISMS BY WHICH CELLS RESPOND AND ADAPT TO MULTIPLE ENVIRONMENTAL STRESSES. THE IDENTIFICATION OF THESE SIGNALS HAS LED TO A GREATER MECHANISTIC UNDERSTANDING OF IBD PATHOGENESIS AND POINTED TO POTENTIALLY NEW THERAPEUTIC TARGETS. A CRITICAL ANALYSIS OF CLINICAL TRIALS AND OF RISK-BENEFIT OF BIOLOGICAL THERAPY WAS PRESENTED. THE PROBLEM OF EPSTEIN-BARR VIRUS (EBV) AND LYMPHOMA IN IBD WAS EXTENSIVELY DISCUSSED. LYMPHOMAS CAN DEVELOP IN INTESTINAL SEGMENTS AFFECTED BY IBD AND ARE IN MOST CASES ASSOCIATED WITH EBV. THE REASONS OF TREATMENT FAILURE WERE ALSO ANALYZED BOTH FROM BASIC AND CLINICAL POINTS OF VIEW. TWO VERY INTERESTING PRESENTATIONS ON THE INTEGRATION OF RESEARCH AND CLINICAL CARE IN THE NEAR FUTURE CLOSED THE MEETING. THESE PRESENTATIONS WERE FOCUSED ON MACROTRENDS AFFECTING HEALTHCARE DELIVERY AND RESEARCH, AND THE NEED TO INNOVATE TRADITIONAL INFRASTRUCTURES TO DEAL WITH THESE CHANGING TRENDS AS WELL AS NEW OPPORTUNITIES TO ACCELERATE SCIENTIFIC KNOWLEDGE.	2010	

16 6288  51 THE POTENTIAL ROLE OF EPIGENETIC MODIFICATIONS ON DIFFERENT FACETS IN THE PERIODONTAL PATHOGENESIS. PERIODONTITIS IS A CHRONIC INFLAMMATORY DISEASE THAT AFFECTS THE SUPPORTING STRUCTURES OF TEETH. IN THE LITERATURE, THE ASSOCIATION BETWEEN THE PATHOGENICITY OF BACTERIA AND ENVIRONMENTAL FACTORS IN THIS REGARD HAVE BEEN EXTENSIVELY EXAMINED. IN THE PRESENT STUDY, WE WILL SHED LIGHT ON THE POTENTIAL ROLE THAT EPIGENETIC CHANGE CAN PLAY ON DIFFERENT FACETS OF ITS PROCESS, MORE PARTICULARLY THE MODIFICATIONS CONCERNING THE GENES INVOLVED IN INFLAMMATION, DEFENSE, AND IMMUNE SYSTEMS. SINCE THE 1960S, THE ROLE OF GENETIC VARIANTS IN THE ONSET AND SEVERITY OF PERIODONTAL DISEASE HAS BEEN WIDELY DEMONSTRATED. THESE MAKE SOME PEOPLE MORE SUSCEPTIBLE TO DEVELOPING IT THAN OTHERS. IT HAS BEEN DOCUMENTED THAT THE WIDE VARIATION IN ITS FREQUENCY FOR VARIOUS RACIAL AND ETHNIC POPULATIONS IS DUE PRIMARILY TO THE COMPLEX INTERPLAY AMONG GENETIC FACTORS WITH THOSE AFFECTING THE ENVIRONMENT AND THE DEMOGRAPHY. IN MOLECULAR BIOLOGY, EPIGENETIC MODIFICATIONS ARE DEFINED AS ANY CHANGE IN THE PROMOTER FOR THE CPG ISLANDS, IN THE STRUCTURE OF THE HISTONE PROTEIN, AS WELL AS POST-TRANSLATIONAL REGULATION BY MICRORNAS (MIRNAS), BEING KNOWN TO CONTRIBUTE TO THE ALTERATION IN GENE EXPRESSION FOR COMPLEX MULTIFACTORIAL DISEASES SUCH AS PERIODONTITIS. THE KEY ROLE OF EPIGENETIC MODIFICATION IS TO UNDERSTAND THE MECHANISM INVOLVED IN THE GENE-ENVIRONMENT INTERACTION, AND THE DEVELOPMENT OF PERIODONTITIS IS NOW THE SUBJECT OF MORE AND MORE STUDIES THAT ATTEMPT TO IDENTIFY WHICH FACTORS ARE STIMULATING IT, BUT ALSO AFFECT THE REDUCED RESPONSE TO THERAPY.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
17 2952  25 GENETIC AND EPIGENETIC ETIOLOGY OF INFLAMMATORY BOWEL DISEASE: AN UPDATE. INFLAMMATORY BOWEL DISEASE (IBD) IS A CHRONIC DISEASE WITH PERIODS OF EXACERBATION AND REMISSION OF THE DISEASE. THE ETIOLOGY OF IBD IS NOT FULLY UNDERSTOOD. MANY STUDIES POINT TO THE PRESENCE OF GENETIC, IMMUNOLOGICAL, ENVIRONMENTAL, AND MICROBIOLOGICAL FACTORS AND THE INTERACTIONS BETWEEN THEM IN THE OCCURRENCE OF IBD. THE REVIEW LOOKS AT GENETIC FACTORS IN THE CONTEXT OF BOTH IBD PREDISPOSITION AND PHARMACOGENETICS.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
18 2984  47 GENETIC DETERMINANTS OF POOR RESPONSE TO TREATMENT IN SEVERE ASTHMA. SEVERE ASTHMA IS A MULTIFACTORIAL DISORDER WITH MARKED PHENOTYPIC HETEROGENEITY AND COMPLEX INTERACTIONS BETWEEN GENETICS AND ENVIRONMENTAL RISK FACTORS, WHICH COULD, AT LEAST IN PART, EXPLAIN WHY DURING STANDARD PHARMACOLOGIC TREATMENT, MANY PATIENTS REMAIN POORLY CONTROLLED AND AT AN INCREASED RISK OF AIRWAY REMODELING AND DISEASE PROGRESSION. THE CONCEPT OF "PRECISION MEDICINE" TO BETTER SUIT INDIVIDUAL UNIQUE NEEDS IS AN EMERGING TREND IN THE MANAGEMENT OF CHRONIC RESPIRATORY DISEASES. OVER THE PAST FEW YEARS, GENOME-WIDE ASSOCIATION STUDIES (GWAS) HAVE REVEALED NOVEL PHARMACOGENETIC VARIANTS RELATED TO RESPONSES TO INHALED CORTICOSTEROIDS AND THE CLINICAL EFFICACY OF BRONCHODILATORS. OPTIMAL CLINICAL RESPONSE TO TREATMENT MAY VARY BETWEEN RACIAL/ETHNIC GROUPS OR INDIVIDUALS DUE TO GENETIC DIFFERENCES. IT IS ALSO PLAUSIBLE TO ASSUME THAT EPIGENETIC FACTORS PLAY A KEY ROLE IN THE MODULATION OF GENE EXPRESSION PATTERNS AND INFLAMMATORY CYTOKINES. REMARKABLY, SPECIFIC GENETIC VARIANTS RELATED TO TREATMENT EFFECTIVENESS MAY INDICATE PROMISING PATHWAYS FOR NOVEL THERAPIES IN SEVERE ASTHMA. IN THIS REVIEW, WE PROVIDE A CONCISE UPDATE OF GENETIC DETERMINANTS OF POOR RESPONSE TO TREATMENT IN SEVERE ASTHMA AND FUTURE DIRECTIONS IN THE FIELD.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
19 3028  39 GENETICS OF COMPLEX AIRWAY DISEASE. THE PAST 3 YEARS HAVE SEEN HIGHLY SIGNIFICANT GENETIC EFFECTS IDENTIFIED FOR A WIDE VARIETY OF COMMON COMPLEX DISEASES, INCLUDING THE AIRWAY DISORDERS OF ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE. IT APPEARS THAT ONLY A PORTION OF THE GENETICALLY MEDIATED SUSCEPTIBILITY TO COMPLEX DISEASES HAS BEEN IDENTIFIED, AND THERE IS MUCH LEFT TO BE DISCOVERED. THIS REVIEW BRIEFLY DESCRIBES THE RESULTS OF THE GENOME-WIDE ASSOCIATION STUDIES OF ASTHMA AND GIVES AN OVERVIEW OF THE PARALLEL AND INCREASINGLY LARGE-SCALE STUDIES THAT ARE TAKING PLACE WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE. THE FUTURE IMPACT IS DISCUSSED OF TECHNOLOGICAL ADVANCES THAT ALLOW INCREASINGLY LARGE-SCALE GENE EXPRESSION STUDIES, NEXT-GENERATION SEQUENCING, AND GENOME-WIDE TESTING FOR EPIGENETIC EFFECTS. THE USE OF GENETIC TECHNOLOGY TO EXAMINE THE AIRWAY MICROBIOTA THAT INTERACT WITH THE MUCOSA IN HEALTH AND DISEASE IS DESCRIBED.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
20 5643  43 SEX AND AUTOIMMUNITY: PROPOSED MECHANISMS OF DISEASE ONSET AND SEVERITY. CHRONIC AUTOIMMUNE DISEASES AFFECT 5-10% OF THE POPULATION WORLDWIDE AND ARE LARGELY PREDOMINANT IN WOMEN. SEX HORMONE CHANGES HAVE BEEN WIDELY INVESTIGATED BASED ON CHANGES IN THE CLINICAL PHENOTYPES OBSERVED DURING PREGNANCY AND MENOPAUSE. IT IS KNOWN THAT FEMALES WITH AUTOIMMUNE DISEASES MANIFEST A HIGHER RATE OF CIRCULATING LEUKOCYTES WITH A SINGLE X CHROMOSOME, AND THERE HAVE BEEN SEVERAL REPORTS ON THE ROLE OF X CHROMOSOME GENE DOSAGE THROUGH INACTIVATION OR DUPLICATION IN AUTOIMMUNITY. HOWEVER, IT IS ALSO IMPORTANT NOT TO OVERLOOK MEN WITH AUTOIMMUNE DISEASES, WHO MIGHT MANIFEST A MORE FREQUENT LOSS OF THE Y CHROMOSOME IN CIRCULATING LEUKOCYTES. AREAS COVERED: IN THE PRESENT REVIEW, WE WILL DISCUSS THE CURRENT EVIDENCE SUPPORTING THE MECHANISMS OF FEMALE PREDOMINANCE IN RHEUMATIC DISEASES, BY DISCUSSING THE ROLE OF REPRODUCTIVE HISTORY, SEX HORMONES AND ABNORMALITIES RELATED TO THEM, CLINICAL DIFFERENCES BETWEEN MALE AND FEMALE PATIENTS, AND EPIGENETIC CHANGES THAT HAVE BEEN EVALUATED THROUGH TWIN STUDIES ON GENETIC AND ENVIRONMENTAL CHANGES IN RHEUMATIC PATIENTS. EXPERT OPINION: THE INFLUENCE OF SEX HORMONES AND CHROMOSOMES ON THE FUNCTION OF THE INNATE AND ADAPTIVE IMMUNE SYSTEMS NEEDS TO BE CLARIFIED, TO BETTER UNDERSTAND THE RISK OF AUTOIMMUNE DISEASES, EARLY DIAGNOSTIC TOOLS, AND THERAPEUTIC RESPONSE.	2019