1 5222 89 PRIMARY BILIARY CIRRHOSIS: FAMILY STORIES. PRIMARY BILIARY CIRRHOSIS (PBC) IS A CHRONIC IMMUNE-MEDIATED CHOLESTATIC LIVER DISEASE OF UNKNOWN AETIOLOGY WHICH AFFECTS MOSTLY WOMEN IN MIDDLE AGE. FAMILIAL PBC IS WHEN PBC AFFECTS MORE THAN ONE MEMBER OF THE SAME FAMILY, AND DATA SUGGEST THAT FIRST-DEGREE RELATIVES OF PBC PATIENTS HAVE AN INCREASED RISK OF DEVELOPING THE DISEASE. MOST OFTEN, THESE FAMILIAL CLUSTERS INVOLVE MOTHER-DAUGHTER PAIRS, WHICH IS CONSISTENT WITH THE FEMALE PREPONDERANCE OF THE DISEASE. THESE CLUSTERS PROVIDE EVIDENCE TOWARDS A GENETIC BASIS UNDERLYING PBC. HOWEVER, CLUSTERS OF NONRELATED INDIVIDUALS HAVE ALSO BEEN REPORTED, GIVING STRENGTH TO AN ENVIRONMENTAL COMPONENT. TWIN STUDIES HAVE DEMONSTRATED A HIGH CONCORDANCE FOR PBC IN MONOZYGOTIC TWINS AND A LOW CONCORDANCE AMONG DIZYGOTIC TWINS. IN CONCLUSION, STUDIES OF PBC IN FAMILIES CLEARLY DEMONSTRATE THAT GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS PLAY A ROLE IN THE DEVELOPMENT OF THE DISEASE.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
2 2512 38 EPIGENETICS AND PRIMARY BILIARY CIRRHOSIS: A COMPREHENSIVE REVIEW AND IMPLICATIONS FOR AUTOIMMUNITY. PRIMARY BILIARY CIRRHOSIS (PBC) IS A CHRONIC INFLAMMATORY AUTOIMMUNE DISEASE THAT DEVELOPS BASED UPON THE INTERACTION OF GENETIC AND ENVIRONMENTAL FACTORS. RECENT GENOME-WIDE ASSOCIATION STUDIES (GWAS) HAVE IDENTIFIED DOZENS OF PREDISPOSING VARIANTS INCLUDING HLA, IL12A, AND CTLA4 BUT HAVE BEEN DISAPPOINTED IN IDENTIFYING A "SMOKING GUN." THESE DISCOVERIES HIGHLIGHT THE IMPORTANCE OF THE GENETIC BACKGROUND INVOLVED IN IMMUNOLOGICAL DYSREGULATION. ALTHOUGH CONCORDANCE RATE OF PBC IN MONOZYGOTIC (MZ) TWINS IS AMONG THE HIGHEST REPORTED IN AUTOIMMUNE DISORDERS, INCOMPLETE DISEASE CONCORDANCE IN TWINS ASSOCIATED WITH DIFFERENTIALLY EXPRESSED GENES HAS BEEN DEMONSTRATED. HOWEVER, LITTLE IS UNDERSTOOD ABOUT HOW ENVIRONMENTAL ASPECTS CONTRIBUTE TO THE DISEASE AND WHY MIDDLE-AGED WOMEN ARE MORE SUSCEPTIBLE. AS A RESULT, EPIGENETIC FACTORS, WHICH CONVERT SIGNALS INDICATING ENVIRONMENTAL CHANGES INTO DYNAMIC AND HERITABLE ALTERATIONS OF TRANSCRIPTIONAL POTENTIAL, ARE GETTING INCREASED ATTENTION BY RESEARCHERS IN BOTH BASIC AND CLINICAL STUDIES. AMONG EPIGENETIC MECHANISMS, THE INSTABILITY AND SKEWED GENE EXPRESSION IN THE X CHROMOSOME MAY ACCOUNT FOR THE FEMALE PREPONDERANCE IN PBC. IN ADDITION, TRANSCRIPTIONAL REGULATION OF HISTONE MODIFICATION AND DNA METHYLATION UNDERSCORES POTENTIAL INVOLVEMENT IN DISEASE PATHOGENESIS. HIGH-THROUGHPUT TECHNIQUES ARE BEING USED TO IDENTIFY EPIGENETIC REGULATORS. IN THIS REVIEW, WE ATTEMPT TO OUTLINE RECENT PROGRESS REGARDING EPIGENETICS IN PBC AND OTHER AUTOIMMUNE DISEASES.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
3 2588 32 EPIGENETICS OF PRIMARY BILIARY CHOLANGITIS. PRIMARY BILIARY CHOLANGITIS (PBC) IS A CHRONIC CHOLESTATIC LIVER DISEASE WITH NON-SUPPURATIVE DESTRUCTION OF THE INTRAHEPATIC BILE DUCTS. THE INTERPLAY OF GENETICS AND ENVIRONMENTAL TRIGGERS CONTRIBUTES TO THE ONSET OF THE DISEASE AND SUBSEQUENTLY RESULTS IN CHOLESTASIS AND PROGRESSIVE FIBROSIS. RECENTLY, GENOME-WIDE ASSOCIATION STUDIES (GWAS) HAVE IDENTIFIED MULTIPLE GENES INFLUENCING THE SUSCEPTIBILITY TO PBC IN HLA AND NON-HLA LOCI. HOWEVER, IT IS ESTIMATED THAT THE KNOWN RISK VARIANTS MERELY ACCOUNT FOR NO MORE THAN 20% OF THE HERITABILITY OF PBC AND CAUSES OF THE REMAINING HERITABILITY REMAIN UNCERTAIN. INCREASING EVIDENCE SUGGESTS THAT THE PRESENCE OF EPIGENETIC ABNORMALITIES MAY EXPLAIN THE "MISSING HERITABILITY" THAT CANNOT BE CAPTURED BY GWAS. AMONG THESE EPIGENETIC MECHANISMS, DNA METHYLATION, HISTONE MODIFICATION, AND NONCODING RNAS (I.E. MIRNA AND LNCRNA) ARE INVOLVED IN THE PATHOGENESIS OF PBC. ADDITIONALLY, TELOMERE DYSREGULATION IN BILIARY EPITHELIAL CELLS (BECS) MAY PLAY A ROLE IN DISEASE ONSET, WHEREAS A DEFICIENCY IN SEX CHROMOSOME AND SKEWED GENE EXPRESSION IN THE X CHROMOSOME MAY TO SOME EXTENT EXPLAIN THE FEMALE DOMINANCE IN PBC.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
4 5506 34 RHEUMATOID ARTHRITIS AND PRIMARY BILIARY CIRRHOSIS: CAUSE, CONSEQUENCE, OR COINCIDENCE? PRIMARY BILIARY CIRRHOSIS (PBC) IS A PROGRESSIVE CHOLESTATIC LIVER DISEASE CHARACTERIZED SEROLOGICALLY BY CHOLESTASIS AND THE PRESENCE OF HIGH-TITRE ANTIMITOCHONDRIAL ANTIBODIES AND HISTOLOGICALLY BY CHRONIC NONSUPPURATIVE CHOLANGITIS AND GRANULOMATA. PBC PATIENTS OFTEN HAVE CONCOMITANT AUTOIMMUNE DISEASES, INCLUDING ARTHROPATHIES. THIS RAISES THE QUESTION AS TO WHETHER THERE ARE SHARED FEATURES IN THE PATHOGENESIS OF THOSE DISEASES WITH THE PATHOGENESIS OF PBC. EPIDEMIOLOGICAL AND LARGE CASE STUDIES HAVE INDICATED THAT ALTHOUGH THE INCIDENCE OF RHEUMATOID ARTHRITIS (RA) IS NOT SIGNIFICANTLY RAISED IN PBC PATIENTS, THERE APPEARS TO BE A HIGHER RATE OF RA IN PBC PATIENTS AND THEIR RELATIVES. GENETIC STUDIES HAVE DEMONSTRATED THAT SEVERAL GENES IMPLICATED IN PBC HAVE ALSO BEEN IMPLICATED IN RA. EPIGENETIC STUDIES PROVIDED A WEALTH OF DATA REGARDING RA, BUT THE FINDINGS ON EPIGENETIC CHANGES IN PBC ARE VERY LIMITED. AS WELL, CERTAIN INFECTIOUS AGENTS IDENTIFIED IN THE PATHOGENESIS OF PBC MAY ALSO PLAY A ROLE IN THE PATHOGENESIS OF RA. THESE DATA SUGGEST THAT ALTHOUGH RA IS NOT SIGNIFICANTLY PRESENT IN PBC, SOME INDIVIDUALS WITH CERTAIN GENETIC TRAITS AND ENVIRONMENTAL EXPOSURES MAY DEVELOP BOTH CONDITIONS. THIS CONCEPT MAY ALSO APPLY TO OTHER CONCOMITANT DISEASES FOUND IN PBC PATIENTS.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
5 3012 30 GENETICS AND EPIGENETICS IN THE PATHOGENESIS OF PRIMARY BILIARY CHOLANGITIS. PRIMARY BILIARY CHOLANGITIS (PBC) IS A CHRONIC, SLOWLY PROGRESSIVE CHOLESTATIC AUTOIMMUNE LIVER DISEASE PREDOMINANTLY AFFLICTING WOMEN. PBC IS CHARACTERIZED BY THE PRESENCE OF DISEASE-SPECIFIC ANTIMITOCHONDRIAL ANTIBODIES AND THE HISTOLOGICAL DESTRUCTION OF INTRAHEPATIC BILE DUCTS, WHICH EVENTUALLY LEAD TO CIRRHOSIS AND HEPATIC FAILURE. FORTUNATELY, URSODEOXYCHOLIC ACID THERAPY HAS IMPROVED THE OUTCOME OF THE VAST MAJORITY OF PBC CASES. ALTHOUGH THE ETIOLOGY OF PBC HAS NOT YET BEEN ELUCIDATED, HUMAN LEUKOCYTE ANTIGEN (HLA) CLASS II ALLELES HAVE BEEN CONSISTENTLY ASSOCIATED WITH DISEASE ONSET FOR DECADES. PBC PATIENTS MAY ALSO HAVE GENETICALLY DETERMINED RISK FACTORS IN NON-HLA REGIONS. MEANWHILE, EXPOSURE TO ENVIRONMENTAL FACTORS, SUCH AS INFECTIOUS DISEASES AND HARMFUL CHEMICALS, CAN PRODUCE EPIGENETIC ALTERATIONS IN SOME INDIVIDUALS AND SUBSEQUENT PBC ONSET. IN THIS REVIEW, WE DESCRIBE THE INFLUENCE OF HLA ALLELES AND OTHER GENE POLYMORPHISMS ON PBC ALONG WITH THE RESULTS OF GENOME-WIDE ASSOCIATION STUDIES ON THIS DISEASE AND ITS FUTURE PROSPECTS IN TERMS OF EPIGENETICS.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
6 3112 39 GEOEPIDEMIOLOGY AND (EPI-)GENETICS IN PRIMARY BILIARY CHOLANGITIS. PRIMARY BILIARY CHOLANGITIS (PBC) IS A RARE FEMALE PREPONDERANT CHRONIC AUTOIMMUNE CHOLESTATIC LIVER DISEASE, CHARACTERIZED BY INTRAHEPATIC DUCTOPENIA AND PROGRESSIVE FIBROSIS. DURING LAST DECADES INCIDENCE AND PREVALENCE SHOWED AN INCREASING RATE WHICH VARY WIDELY WORLDWIDE DEMONSTRATING AN IMPORTANT INTERACTION BETWEEN ENVIRONMENTAL AND GENETIC FACTORS. HERITABILITY SUGGESTED BY FAMILIAL OCCURRENCE AND MONOZYGOTIC TWINS CONCORDANCE HAVE BEEN CONFIRMED IN MORE STUDIES. EPIGENETICS MECHANISMS SUCH AS HISTONE MODIFICATION AND DNA METHYLATION CAN PARTIALLY EXPLAIN PREDISPOSITION AND INHERITANCE OF THIS DISEASE. NEVERTHELESS, AN ASSOCIATION WITH SPECIFIC CLASS II HUMAN LEUKOCYTE ANTIGEN (HLA) VARIANTS HAVE BEEN REPORTED, SHOWING AN INCREASE RISK IN SUSCEPTIBILITY. MORE RECENTLY, DATA REGARDING A STRONG PROTECTIVE ASSOCIATION BETWEEN PBC AND HLA ALLELES CONFIRMED THIS ASSOCIATION. AFTER RECENT GENOME-WIDE ASSOCIATION STUDIES (GWAS), A MORE INTRICATE INTERACTION BETWEEN PBC AND THE HLA REGION HAS BEEN SHOWN. FURTHERMORE, GWAS ALSO IDENTIFIED SEVERAL IMMUNE-RELATED-GENES IMPLICATED. MORE GENOME-WIDE ASSOCIATION STUDIES ON THIS DISEASE ARE NEEDED TO REACH A COMPLETE AND SYSTEMATIC KNOWLEDGE OF THIS DISEASE. IN THIS REVIEW WE DISCUSS MORE RECENT ISSUED DATA ON GEOEPIDEMIOLOGY OF PBC AND THE ROLE OF (EPI-)GENETIC MECHANISMS IN ITS PATHOGENESIS.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
7 5220 28 PRIMARY BILIARY CHOLANGITIS: A TALE OF EPIGENETICALLY-INDUCED SECRETORY FAILURE? PRIMARY BILIARY CHOLANGITIS (PBC) IS A CHRONIC CHOLESTATIC LIVER DISEASE ASSOCIATED WITH AUTOIMMUNE-RELATED DESTRUCTION OF SMALL TO MEDIUM SIZE INTRAHEPATIC BILE DUCTS. THE AETIOLOGY OF PBC IS UNKNOWN AND ITS PATHOGENESIS REMAINS OBSCURE. BOTH GENETIC VARIANTS AND ENVIRONMENTAL FACTORS HAVE BEEN LINKED TO INCREASED PBC SUSCEPTIBILITY, WITH OTHER ALTERATIONS KNOWN TO COOPERATE IN DISEASE PATHOBIOLOGY. INCREASING EVIDENCE INDICATES THE PRESENCE OF EPIGENETIC ABNORMALITIES IN PBC, PARTICULARLY ALTERATIONS OF CHOLANGIOCELLULAR MICRORNAS (MIRNAS OR MIRS). THIS REVIEW HIGHLIGHTS AND DISCUSSES THE MOST RELEVANT EPIGENETIC ALTERATIONS FOUND IN PATIENTS WITH PBC, FOCUSING ON THE ROLE OF MIR-506 IN THE PROMOTION OF CHOLESTASIS AND IMMUNE ACTIVATION.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
8 5146 35 POTENTIAL ROLES FOR INFECTIOUS AGENTS IN THE PATHOPHYSIOLOGY OF PRIMARY BILIARY CIRRHOSIS: WHAT'S NEW? PRIMARY BILIARY CIRRHOSIS (PBC) IS A PROGRESSIVE CHOLESTATIC LIVER DISEASE SEROLOGICALLY CHARACTERIZED BY THE PRESENCE OF HIGH-TITER ANTIMITOCHONDRIAL ANTIBODIES AND, HISTOLOGICALLY BY CHRONIC NONSUPPURATIVE CHOLANGITIS AND GRANULOMATA. THE AETIOLOGY OF THE DISEASE REMAINS ELUSIVE, ALTHOUGH GENETIC, EPIGENETIC, ENVIRONMENTAL, AND INFECTIOUS FACTORS HAVE BEEN CONSIDERED IMPORTANT FOR THE INDUCTION OF THE DISEASE IN GENETICALLY PRONE INDIVIDUALS. THE DISEASE SHOWS A STRIKING FEMALE PREDOMINANCE AND BECOMES CLINICALLY OVERT AT THE FOURTH TO SIXTH DECADE. THESE CHARACTERISTICS HAVE PROMPTED INVESTIGATORS TO CONSIDER INFECTIONS THAT PREDOMINATE IN WOMEN AT THESE AGES AS THE LIKELY CANDIDATES FOR TRIGGERING THE DISEASE. RECURRENT URINARY TRACT INFECTIONS DUE TO ESCHERICHIA COLI WERE THE FIRST INFECTIONS TO BE CONSIDERED PATHOGENETICALLY RELEVANT. OVER THE YEARS, SEVERAL OTHER MICROORGANISMS HAVE BEEN LINKED TO THE PATHOGENESIS OF PBC OWING TO EPIDEMIOLOGICAL, IMMUNOLOGICAL, MICROBIOLOGICAL, OR EXPERIMENTAL FINDINGS IN ANIMAL MODELS. RECENT STUDIES HAVE PROVIDED DATA SUPPORTING THE PATHOGENIC ROLE OF NOVOSPHINGOBIUM AROMATICIVORANS AND BETARETROVIRUSES. SEVERAL REPORTS HAVE LINKED OTHER ORGANISMS TO THE INDUCTION OF THE DISEASE AND/OR THE MAINTENANCE OF THE AUTO-AGGRESSIVE RESPONSES THAT ARE PERPETUATED OVER THE COURSE OF THE DISEASE. THIS REVIEW HIGHLIGHTS THE FINDINGS OF THE MOST RECENT STUDIES INVESTIGATING THE LINK BETWEEN INFECTIONS AND PBC. WE ALSO DISCUSS THE CLOSE INTERPLAY OF THE INFECTIOUS AGENTS WITH OTHER ENVIRONMENTAL AND GENETIC FACTORS, WHICH MAY EXPLAIN THE MULTIFACETED NATURE OF THIS PUZZLING DISEASE.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
9 3690 39 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
10  738 24 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
11 5643 27 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
12 2075 28 EPIGENETIC DIFFERENCES IN INFLAMMATION GENES OF MONOZYGOTIC TWINS ARE RELATED TO PARENT-CHILD EMOTIONAL AVAILABILITY AND HEALTH. THE INFLAMMATORY RESPONSE IS AN IMMUNE DEFENSE ENGAGED IMMEDIATELY AFTER INJURY OR INFECTION. CHRONIC INFLAMMATION CAN BE DELETERIOUS FOR VARIOUS HEALTH OUTCOMES AND IS CHARACTERIZED BY HIGH LEVELS OF PRO-INFLAMMATORY MARKERS SUCH AS C-REACTIVE PROTEIN (CRP), INTERLEUKIN 6 (IL-6), AND TUMOR NECROSIS FACTOR ALPHA (TNF-ALPHA). A LARGE BODY OF RESEARCH DEMONSTRATES THESE INFLAMMATORY MARKERS ARE RESPONSIVE TO STRESS AND QUALITY OF SOCIAL RELATIONSHIPS THROUGHOUT THE LIFESPAN. FOR EXAMPLE, THE QUALITY OF THE EARLY PARENTAL BOND PREDICTS VARIOUS HEALTH OUTCOMES AND MAY BE DRIVEN BY CHANGES IN IMMUNE FUNCTION. EPIGENETIC PROCESSES, SUCH AS DNA METHYLATION, MAY BE ONE MECHANISM BY WHICH EARLY SOCIAL EXPERIENCES SHAPE IMMUNE FUNCTIONING. THE PRESENT STUDY USED A MONOZYGOTIC TWIN DIFFERENCE DESIGN TO ASSESS IF MOTHER-REPORTED EMOTIONAL AVAILABILITY AT 1 YEAR AND 2.5 YEARS PREDICTED IMMUNE GENE METHYLATION AT 8 YEARS OF AGE. FURTHER, WE ASSESSED IF INFLAMMATION GENE METHYLATION WAS RELATED TO GENERAL HEALTH PROBLEMS (E.G. INFECTIONS, ALLERGIES, ETC.). WE FOUND THAT MOTHER-REPORTED EMOTIONAL AVAILABILITY AT 1 YEAR, BUT NOT 2.5 YEARS, WAS RELATED TO METHYLATION OF VARIOUS IMMUNE GENES IN MONOZYGOTIC TWINS. FURTHERMORE, TWIN PAIRS DISCORDANT IN HEALTH PROBLEMS HAVE MORE DIFFERENCE IN IMMUNE GENE METHYLATION COMPARED TO TWIN PAIRS CONCORDANT FOR HEALTH PROBLEMS, SUGGESTING THAT METHYLATION OF IMMUNE GENES MAY HAVE FUNCTIONAL CONSEQUENCES FOR GENERAL HEALTH. THESE RESULTS SUGGEST THAT THE EMOTIONAL COMPONENT OF ATTACHMENT QUALITY DURING INFANCY CONTRIBUTES TO IMMUNE EPIGENETIC PROFILES IN CHILDHOOD, WHICH MAY INFLUENCE GENERAL HEALTH.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
13 2192 27 EPIGENETIC METHODS AND TWIN STUDIES. GENOMIC PREDISPOSITION FAILS TO FULLY EXPLAIN THE ONSET OF COMPLEX DISEASES, WHICH IS WELL ILLUSTRATED BY THE LARGELY INCOMPLETE CONCORDANCE AMONG MONOZYGOTIC TWINS. EPIGENETIC MECHANISMS, INCLUDING DNA METHYLATION, CHROMATIN REMODELING, AND NON-CODING RNA, ARE THE LINK BETWEEN ENVIRONMENTAL STIMULI AND DISEASE ONSET ON A PERMISSIVE GENETIC BACKGROUND IN AUTOIMMUNE AND CHRONIC INFLAMMATORY DISEASES. AUTOIMMUNE DISEASES NOW INCLUDE ALMOST 100 CONDITIONS AND ARE ESTIMATED TO CUMULATIVELY AFFECT UP TO 5% OF THE WORLD POPULATION WITH A HEALTHCARE EXPENDITURE SUPERIOR TO CANCER WORLDWIDE. MANY ADVANCES IN MEDICINE HAVE BEEN MADE TO TREAT THESE CONDITIONS BUT THERE ARE STILL GAPS, AND AN INNOVATIVE AND EFFICIENT THERAPY IS NEEDED. SYSTEMIC AUTOIMMUNE DISEASES INCLUDE RHEUMATOID ARTHRITIS, SYSTEMIC LUPUS ERYTHEMATOSUS, SYSTEMIC SCLEROSIS, SJOGREN SYNDROME, POLYMYOSITIS, AND DERMATOMYOSITIS. MONOZYGOTIC TWINS DISCORDANT FOR ANY DISEASE OFFER AN IDEAL STUDY DESIGN AS THEY ARE MATCHED FOR MANY FACTORS, INCLUDING GENETIC VARIATION AND THIS IS A REAL ADVANTAGE FOR EPIGENETICS STUDY. WE WILL HEREIN DISCUSS THE AVAILABLE DATA IN THE EPIGENETIC DIFFERENCES LEADING TO DISEASE DISCORDANCE IN MZ TWINS FOR SYSTEMIC LUPUS ERYTHEMATOSUS, RHEUMATOID ARTHRITIS, AND SYSTEMIC SCLEROSIS.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
14 2107 26 EPIGENETIC FACTORS IN SCHIZOPHRENIA: MECHANISMS AND EXPERIMENTAL APPROACHES. SCHIZOPHRENIA IS A CHRONIC MENTAL DISORDER THAT IS STILL POORLY UNDERSTOOD DESPITE DECADES OF STUDY. MANY FACTORS HAVE BEEN FOUND TO CONTRIBUTE TO THE PATHOGENESIS, INCLUDING NEURODEVELOPMENTAL DISTURBANCE, GENETIC RISK, AND ENVIRONMENTAL INSULT, BUT NO SINGLE ROOT CAUSE HAS EMERGED. WHILE EVIDENCE FROM TWIN STUDIES SUGGESTS A STRONG HERITABLE COMPONENT, FEW INDIVIDUAL LOCI HAVE BEEN IDENTIFIED IN GENOMEWIDE SCREENS, SUGGESTING A ROLE FOR EPIGENETIC EFFECTS. RATHER, LARGE NUMBERS OF WEAKLY ACTING LOCI MAY CUMULATIVELY INCREASE DISEASE RISK, INCLUDING SEVERAL MAPPING TO EPIGENETIC PATHWAYS. IN THIS REVIEW, WE DISCUSS MECHANISMS OF EPIGENETIC REGULATION AND EVIDENCE FOR AN EPIGENETIC CONTRIBUTION TO DISEASE PHENOTYPE. WE FURTHER DESCRIBE THE RANGE OF EXPERIMENTAL TOOLS CURRENTLY AVAILABLE TO STUDY EPIGENETIC EFFECTS ASSOCIATED WITH THE DISEASE.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
15 2945 24 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
16 6262 29 THE MULTIFACETED FUNCTIONAL ROLE OF DNA METHYLATION IN IMMUNE-MEDIATED RHEUMATIC DISEASES. GENOMIC PREDISPOSITION CANNOT EXPLAIN THE ONSET OF COMPLEX DISEASES, AS WELL ILLUSTRATED BY THE LARGELY INCOMPLETE CONCORDANCE AMONG MONOZYGOTIC TWINS. EPIGENETIC MECHANISMS, INCLUDING DNA METHYLATION, CHROMATIN REMODELLING AND NON-CODING RNA, ARE CONSIDERED TO BE THE LINK BETWEEN ENVIRONMENTAL STIMULI AND DISEASE ONSET ON A PERMISSIVE GENETIC BACKGROUND IN AUTOIMMUNE AND CHRONIC INFLAMMATORY DISEASES. THE PARADIGMATIC CASES OF RHEUMATOID ARTHRITIS (RA), SYSTEMIC LUPUS ERYTHEMATOSUS (SLE), SYSTEMIC SCLEROSIS (SSC), SJOGREN'S SYNDROME (SJS) AND TYPE-1 DIABETES (T1D) SHARE THE LOSS OF IMMUNOLOGICAL TOLERANCE TO SELF-ANTIGEN INFLUENCED BY SEVERAL FACTORS, WITH A LARGELY INCOMPLETE ROLE OF INDIVIDUAL GENOMIC SUSCEPTIBILITY. THE MOST WIDELY INVESTIGATED EPIGENETIC MECHANISM IS DNA METHYLATION WHICH IS ASSOCIATED WITH GENE SILENCING AND IS DUE TO THE BINDING OF METHYL-CPG BINDING DOMAIN (MBD)-CONTAINING PROTEINS, SUCH AS MECP2, TO 5-METHYLCYTOSINE (5MC). INDEED, A CAUSAL RELATIONSHIP OCCURS BETWEEN DNA METHYLATION AND TRANSCRIPTION FACTORS OCCUPANCY AND RECRUITMENT AT SPECIFIC GENOMIC LOCUS. IN MOST CASES, THE RESULTS OBTAINED IN DIFFERENT STUDIES ARE CONTROVERSIAL IN TERMS OF DNA METHYLATION COMPARISON WHILE FASCINATING EVIDENCE COMES FROM THE COMPARISON OF THE EPIGENOME IN CLINICALLY DISCORDANT MONOZYGOTIC TWINS. IN THIS MANUSCRIPT, WE WILL REVIEW THE MECHANISMS OF EPIGENETICS AND DNA METHYLATION CHANGES IN SPECIFIC IMMUNE-MEDIATED RHEUMATIC DISEASES TO HIGHLIGHT REMAINING UNMET NEEDS AND TO IDENTIFY POSSIBLE SHARED MECHANISMS BEYOND DIFFERENT TISSUE INVOLVEMENTS WITH COMMON THERAPEUTIC OPPORTUNITIES. KEY POINTS * DNA METHYLATION HAS A CRUCIAL ROLE IN REGULATING AND TUNING THE IMMUNE SYSTEM. * EVIDENCES SUGGEST THAT DYSREGULATION OF DNA METHYLATION IS PIVOTAL IN THE CONTEXT OF IMMUNE-MEDIATED RHEUMATIC DISEASES. * DNA METHYLATION DYSREGULATION IN FOXP3 AND INTERFERONS-RELATED GENES IS SHARED WITHIN SEVERAL AUTOIMMUNE DISEASES. * DNA METHYLATION IS AN ATTRACTIVE MARKER FOR DIAGNOSIS AND THERAPY.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
17 3027 29 GENETICS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS A COMPLEX DISEASE WITH MULTIFACTORIAL BACKGROUND, BASED ON THE INTERACTION OF ENVIRONMENTAL AND GENETIC FACTORS. ENVIRONMENTAL FACTORS ARE CLEARLY RELATED TO THE DEVELOPMENT OF THE DISEASE. HOWEVER, FAMILY AND TWIN STUDIES SUGGESTED GENETICS FACTORS TO BE ONE OF THE IMPORTANT DETERMINANTS FOR THE DEVELOPMENT OF COPD. DIFFERENT APPROACHES HAVE BEEN USED TO IDENTIFY GENES OF INTEREST. GENOMEWIDE LINKAGE ANALYSIS FOUND AREAS OF INTEREST ON DIFFERENT CHROMOSOMES, WITH SOME GENES LOCATED IN THIS REGIONS BEING IDENTIFIED AND REPLICATED AS SUSCEPTIBILITY GENES. NUMEROUS OF CANDIDATE GENES THAT COULD BE LINKED TO DISEASE PATHOGENESIS HAVE BEEN IMPLICATED IN COPD GENETICS. HOWEVER, THE CANDIDATE GENE APPROACH IS OFTEN LIMITED BY INCONSISTENT RESULTS IN OTHER STUDY POPULATIONS. RECENTLY, A COMBINATION OF DIFFERENT METHODS IS USED GIVING MORE EVIDENCE FOR SOME CANDIDATE GENES, INCLUDING TGFBETA-1, SURFACTANT, SERPINE2 AND MICROSOMAL EPOXIDE HYDROLASE. IN THE FUTURE ONGOING EXACT PHENOTYPE DEFINITION, COMBINATION OF SEVERAL APPROACHES, GENOME-WIDE ASSOCIATION STUDIES AND ANIMAL MODEL GENETICS WILL LEAD TO NEW INSIGHTS INTO THE GENETICS OF COPD, WITH EPIGENETIC FACTORS NEEDS TO BE FURTHER INVESTIGATED AND CONSIDERED IN CONCERT WITH GENETIC FINDINGS.	2007	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
18 1844 30 EFFECTS OF THE LIFESTYLE HABITS IN BREAST CANCER TRANSCRIPTIONAL REGULATION. THROUGH RESEARCH CARRIED OUT IN THE LAST 25 YEARS ABOUT THE BREAST CANCER ETIOLOGY, IT HAS BEEN POSSIBLE TO ESTIMATE THAT LESS THAN 10 % OF PATIENTS WHO ARE DIAGNOSED WITH THE CONDITION ARE CARRIERS OF SOME GERMLINE OR SOMATIC MUTATION. THE CLINICAL REPORTS OF BREAST CANCER PATIENTS WITH HEALTHY TWINS AND THE DEVELOPMENT OF DISEASE IN WOMEN WITHOUT HIGH PENETRANCE MUTATIONS DETECTED, WARN THE PARTICIPATION MORE FACTORS IN THE TRANSFORMATION PROCESS. THE HIGH INCIDENCE OF MAMMARY ADENOCARCINOMA IN THE MODERN WOMAN AND THE URGENT NEED FOR NEW METHODS OF PREVENTION AND EARLY DETECTION HAVE DEMANDED MORE INFORMATION ABOUT THE ROLE THAT ENVIRONMENT AND LIFESTYLE HAVE ON THE TRANSFORMATION OF MAMMARY GLAND EPITHELIAL CELLS. OBESITY, ALCOHOLISM AND SMOKING ARE FACTORS THAT HAVE SHOWN A CLOSE CORRELATION WITH THE RISK OF DEVELOPING BREAST CANCER. AND ALTHOUGH THESE CONDITIONS AFFECT DIFFERENT CELL REGULATION LEVELS, THE STUDY OF ITS EFFECTS IN THE MECHANISMS OF TRANSCRIPTIONAL AND EPIGENETIC REGULATION IS CONSIDERED CRITICAL FOR A BETTER UNDERSTANDING OF THE LOSS OF IDENTITY OF EPITHELIAL CELLS DURING CARCINOGENESIS OF THIS TISSUE. THE MAIN OBJECTIVE OF THIS REVIEW WAS TO ESTABLISH THE IMPORTANCE OF CHANGES OCCURRING TO TRANSCRIPTIONAL LEVEL IN THE MAMMARY GLAND AS A CONSEQUENCE OF ACUTE OR CHRONIC EXPOSURE TO HARMFUL PRODUCTS SUCH AS OBESITY-CAUSING FOODS, ETHANOL AND CIGARETTE SMOKE COMPONENTS. AT ANALYZE THE MAIN STUDIES RELATED TO TOPIC, IT HAS CONCLUDED THAT THE UNDERSTANDING OF EFFECTS CAUSED BY THE LIFESTYLE FACTORS IN PERFORMANCE OF THE TRANSCRIPTIONAL MECHANISMS THAT DETERMINE GENE EXPRESSION OF THE MAMMARY GLAND EPITHELIAL CELLS, MAY HELP EXPLAIN THE DEVELOPMENT OF THIS DISEASE IN WOMEN WITHOUT GENETIC PROPENSITY AND DIFFERENT PHENOTYPIC MANIFESTATIONS OF THIS CANCER TYPE.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
19 3743 37 INSIGHTS FROM GENOMIC STUDIES ON THE ROLE OF SEX STEROIDS IN THE AETIOLOGY OF ENDOMETRIOSIS. ENDOMETRIOSIS IS A CHRONIC NEURO-INFLAMMATORY DISORDER THE DEFINING FEATURE OF WHICH IS THE GROWTH OF TISSUE (LESIONS) THAT RESEMBLES THE ENDOMETRIUM OUTSIDE THE UTERUS. ESTIMATES OF PREVALENCE QUOTE RATES OF ~10% OF WOMEN OF REPRODUCTIVE AGE, EQUATING TO AT LEAST 190 MILLION WOMEN WORLD-WIDE. GENETIC, HORMONAL AND IMMUNOLOGICAL FACTORS HAVE ALL BEEN PROPOSED AS CONTRIBUTING TO RISK FACTORS ASSOCIATED WITH THE DEVELOPMENT OF LESIONS. TWIN STUDIES REPORT THE HERITABLE COMPONENT OF ENDOMETRIOSIS AS ~50%. GENOME-WIDE ASSOCIATION STUDIES (GWAS) HAVE IDENTIFIED SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) THAT APPEAR OVER-REPRESENTED IN PATIENTS WITH ENDOMETRIOSIS, PARTICULARLY THOSE WITH MORE EXTENSIVE DISEASE (STAGE III/IV). IN DIFFERENT SAMPLE POPULATIONS, THERE HAS BEEN REPLICATION OF SNPS NEAR GENES INVOLVED IN OESTROGEN AND OTHER STEROID REGULATED PATHWAYS INCLUDING ESR1 (OESTROGEN RECEPTOR ALPHA), GREB1, HOXA10, WNT4 AND MAPK KINASE SIGNALLING. COMPARISONS WITH GWAS CONDUCTED ON OTHER PATIENT COHORTS HAVE FOUND LINKS WITH REPRODUCTIVE TRAITS (AGE AT MENARCHE) AND DISORDERS (FIBROIDS, ENDOMETRIAL AND OVARIAN CANCER) AND COMMON CO-MORBIDITIES (MIGRAINE, DEPRESSION, ASTHMA). IN SUMMARY, GENETIC ANALYSES HAVE PROVIDED NEW INSIGHTS INTO THE HORMONE-REGULATED PATHWAYS THAT MAY CONTRIBUTE TO INCREASED RISK OF DEVELOPING ENDOMETRIOSIS SOME OF WHICH MAY ACT IN EARLY LIFE. NEW STUDIES ARE NEEDED TO CLARIFY THE RELATIONSHIP BETWEEN THE MANY SNPS IDENTIFIED, THE GENES THAT THEY REGULATE AND THEIR CONTRIBUTION(S) TO DEVELOPMENT OF DIFFERENT FORMS OF ENDOMETRIOSIS. WE HOPE THAT MORE ADVANCED METHODS ALLOWING INTEGRATION BETWEEN GWAS, EPIGENETIC AND TISSUE EXPRESSION DATA WILL IMPROVE RISK ANALYSIS AND REDUCE DIAGNOSITIC DELAY. LAY SUMMARY: ENDOMETRIOSIS IS A DEBILITATING REPRODUCTIVE DISORDER AFFECTING ~10% OF REPRODUCTIVE-AGE WOMEN, AND THOSE ASSIGNED FEMALE AT BIRTH, WHICH CAUSES A RANGE OF SYMPTOMS INCLUDING CHRONIC PAIN AND INFERTILITY. THE REASON WHY SOME, BUT NOT ALL THESE INDIVIDUALS, DEVELOP THE LESIONS THAT CHARACTERISE THE DISEASE ARE POORLY UNDERSTOOD, BUT RECENTLY ATTENTION HAS FOCUSED ON GENETIC RISK FACTORS TO EXPLAIN WHY THE INCIDENCE IS HIGHER IN SOME FAMILIES. STUDIES ON LARGE COHORTS OF PATIENTS WITH COMPARISON OF THEIR DNA TO WOMEN WITHOUT ENDOMETRIOSIS OR WITH OTHER DISORDERS HAVE DOCUMENTED CHANGES IN GENES ASSOCIATED WITH STEROID HORMONE PRODUCTION OR ACTION. THE RESULTS PROVIDE FURTHER EVIDENCE THAT ENDOMETRIOSIS SHARES GENETIC RISK FACTORS WITH OTHER DISORDERS OF THE REPRODUCTIVE SYSTEM AND A PLATFORM FOR NEW IDEAS RELATED TO RISK, BIOMARKERS AND THERAPIES.	2022	

20 6791 21 [DOES THE NUMBER OF PATIENTS WITH AUTOIMMUNE DISORDERS AND THE FREQUENCY OF AUTOIMMUNE DISEASES INCREASE?]. AUTOIMMUNE DISEASES GENERALLY BELONG TO THE RARE DISEASES, HOWEVER, SOME OF THEM ARE FREQUENT IN THE POPULATION. IN THE PRESENT WORK THE AUTHORS ANALYSE WHETHER CAN ANY INCREASE BE OBSERVED IN THE NUMBER OF PATIENTS SUFFERING FROM AUTOIMMUNE DISEASES AND WHETHER DO THE FREQUENCY OF CERTAIN AUTOIMMUNE DISORDERS INCREASE. DUE MAINLY TO EPIGENETIC FACTORS THE INCIDENCE OF AUTOIMMUNE DISEASES ARE INCREASING, THEREFORE THERE ARE MORE PATIENTS RECOGNISED WITH PARTICULAR DISORDERS. ON THE OTHER HAND THE INCIDENCE IS INCREASED BY IMPROVING DIAGNOSTIC POSSIBILITIES, BY THE USE OF MORE SPECIFIC AND SENSITIVE CLASSIFICATION CRITERIA AND MORE SOPHISTICATED LABORATORY TESTS, RESULTED IN THE RECOGNITION OF MILDER AND ATYPICAL DISEASE VARIANTS AS WELL. THE PREVALENCE IS ALSO INCREASING IN CONSEQUENCE OF NOVEL IMMUNE SUPPRESSIVE THERAPEUTIC POSSIBILITIES AND THE CONSEQUENT IMPROVEMENT OF SURVIVAL IN THE MOST OF THESE DISEASES. BESIDES, MORE AND MORE DISEASES HAVE BEEN REVEALED TO HAVE AUTOIMMUNE BACKGROUND, AND LOT OF NEW AUTOIMMUNE SYNDROMES, DISEASES HAVE BEEN CHARACTERISED RECENTLY. THIS INCREASES THE NUMBER OF THE KNOWN AUTOIMMUNE RHEUMATIC DISORDERS WITH A CONSEQUENT INCREASE IN THE NUMBER OF AUTOIMMUNE PATIENTS. ASSIGNED TO THE INCREASING NUMBER OF VARIABLE CHRONIC AUTOIMMUNE DISORDERS, AND THE INCREASING NUMBER OF DISABLED PATIENTS WITH SUCH DISEASES INCREASING MEDICAL AND SOCIAL ATTENTION HAS TO BE FOCUSED ON.	2007