1 2919 120 GENE-GENE AND GENE-ENVIRONMENT INTERACTIONS DEFINING LIPID-RELATED TRAITS. PURPOSE OF REVIEW: STEPS TOWARDS REDUCING CHRONIC DISEASE PROGRESSION ARE CONTINUOUSLY BEING TAKEN THROUGH THE FORM OF GENOMIC RESEARCH. STUDIES OVER THE LAST YEAR HAVE HIGHLIGHTED MORE AND MORE POLYMORPHISMS, PATHWAYS AND INTERACTIONS RESPONSIBLE FOR METABOLIC DISORDERS SUCH AS CARDIOVASCULAR DISEASE, OBESITY AND DYSLIPIDEMIA. RECENT FINDINGS: MANY OF THESE CHRONIC ILLNESSES CAN BE PARTIALLY BLAMED BY ALTERED LIPID METABOLISM, COMBINED WITH INDIVIDUAL GENETIC COMPONENTS. CRITICAL EVALUATION AND COMPARISON OF THESE RECENT STUDIES IS ESSENTIAL IN ORDER TO COMPREHEND THE RESULTS, CONCLUSIONS AND FUTURE PROSPECTS IN THE FIELD OF GENOMICS AS A WHOLE. RECENT LITERATURE ELUCIDATES SIGNIFICANT GENE--DIET AND GENE--ENVIRONMENT INTERACTIONS RESULTING IN ALTERED LIPID METABOLISM, INFLAMMATION AND OTHER METABOLIC IMBALANCES LEADING TO CARDIOVASCULAR DISEASE AND OBESITY. SUMMARY: EPIGENETIC AND EPISTATIC INTERACTIONS ARE NOW BECOMING MORE SIGNIFICANTLY ASSOCIATED WITH SUCH DISORDERS, AS GENOMIC RESEARCH DIGS DEEPER INTO THE COMPLEX NATURE OF GENETIC INDIVIDUALITY AND HERITABILITY. THE VAST ARRAY OF DATA COLLECTED FROM GENOME-WIDE ASSOCIATION STUDIES MUST NOW BE EMPOWERED AND EXPLORED THROUGH MORE COMPLEX INTERACTION STUDIES, USING STANDARDIZED METHODS AND LARGER SAMPLE SIZES. IN DOING SO THE ETIOLOGY OF CHRONIC DISEASE PROGRESSION WILL BE FURTHER UNDERSTOOD. 2011 2 2136 30 EPIGENETIC INFLUENCES IN THE OBESITY/COLORECTAL CANCER AXIS: A NOVEL THERAGNOSTIC AVENUE. THE WORLD HEALTH ORGANIZATION (WHO) CONSIDERS THAT OBESITY HAS REACHED PROPORTIONS OF PANDEMIC. EXPERTS ALSO INSIST ON THE IMPORTANCE OF CONSIDERING OBESITY AS A CHRONIC DISEASE AND ONE OF THE MAIN CONTRIBUTORS TO THE WORLDWIDE BURDEN OF OTHER NONTRANSMISSIBLE CHRONIC DISEASES, WHICH HAVE A GREAT IMPACT ON HEALTH, LIFESTYLE, AND ECONOMIC COST. ONE OF THE MOST CURRENT CHALLENGES OF BIOMEDICAL SCIENCE FACES IS TO UNDERSTAND THE ORIGIN OF THE CHRONIC NONTRANSMISSIBLE DISEASES, SUCH AS OBESITY AND CANCER. THERE IS A LARGE EVIDENCE, BOTH IN EPIDEMIOLOGICAL STUDIES IN HUMANS AND IN ANIMAL MODELS, OF THE ASSOCIATION BETWEEN OBESITY AND AN INCREASED RISK OF CANCER INCIDENCE. IN THE LAST YEARS, THE INITIAL DISCOVERY OF EPIGENETIC MECHANISMS REPRESENTS THE MOST RELEVANT FINDING TO EXPLAIN HOW THE GENOME INTERACTS WITH ENVIRONMENTAL FACTORS AND THE RIPPLE EFFECTS ON DISEASE PATHOGENESES. SINCE THEN, ALL EPIGENETIC PROCESS HAS BEEN INVESTIGATED BY THE SCIENTIFIC COMMUNITIES FOR NEARLY TWO DECADES TO DETERMINE WHICH COMPONENTS ARE INVOLVED IN THIS PROCESS. DNA/RNA METHYLATION AND MIRNA ARE CLASSIFIED AS TWO OF THE MOST IMPORTANT REPRESENTATIVE CLASSES OF SUCH EPIGENETIC MECHANISMS AND DYSREGULATED ACTIVITY OF SUCH MECHANISM CAN CERTAINLY CONTRIBUTE TO DISEASE PATHOGENESIS AND/OR PROGRESSION ESPECIALLY IN TUMORS. THIS REVIEW ARTICLE SERVES TO HIGHLIGHT THE IMPACT OF DNA/RNA METHYLATION AND MIRNA-BASED EPIGENETIC MECHANISM ACTIVITIES IN THE INTERPLAY BETWEEN OBESITY AND THE DEVELOPMENT AND CLINICAL SIGNIFICANCE OF COLORECTAL CANCER. 2019 3 6459 21 TIME TO CHANGE FROM A SIMPLE LINEAR MODEL TO A COMPLEX SYSTEMS MODEL. A SIMPLE LINEAR MODEL TO TEST THE HYPOTHESIS BASED ON ONE-ON-ONE RELATIONSHIP HAS BEEN USED TO FIND THE CAUSATIVE FACTORS OF DISEASES. HOWEVER, WE NOW KNOW THAT NOT JUST ONE, BUT MANY FACTORS FROM DIFFERENT SYSTEMS SUCH AS CHEMICAL EXPOSURE, GENES, EPIGENETIC CHANGES, AND PROTEINS ARE INVOLVED IN THE PATHOGENESIS OF CHRONIC DISEASES SUCH AS DIABETES MELLITUS. SO, WITH AVAILABILITY OF MODERN TECHNOLOGIES TO UNDERSTAND THE INTRICATE NATURE OF RELATIONS AMONG COMPLEX SYSTEMS, WE NEED TO MOVE FORWARD TO THE FUTURE BY TAKING COMPLEX SYSTEMS MODEL. 2016 4 3020 33 GENETICS AND EPIGENETICS OF OSTEOARTHRITIS. OSTEOARTHRITIS (OA) IS A COMMON AGE-RELATED DISEASE THAT AFFECTS THE TISSUES OF THE SYNOVIAL JOINT, LEADING TO LOSS OF FUNCTION AND PAIN. IT IMPACTS ON BOTH PATIENT MORBIDITY AND MORTALITY. IT IS A COMPLEX, POLYGENIC DISEASE THAT LACKS ANY LARGE-EFFECT SUSCEPTIBILITY LOCI. INSTEAD, OA SUSCEPTIBILITY ALLELES INDIVIDUALLY CONTRIBUTE ONLY MODESTLY TO THE OVERALL DISEASE RISK, MAKING THEIR IDENTIFICATION CHALLENGING. DESPITE THIS, BREAKTHROUGHS HAVE OCCURRED WITH COMPELLING ASSOCIATIONS SO FAR REPORTED TO POLYMORPHISMS WITHIN THE GENES GDF5 AND MCF2L AND TO THE GENOMIC REGION 7Q22. THE LATTER TWO HAVE EMERGED FROM GENOME-WIDE ASSOCIATION SCANS, WHICH ARE LIKELY TO YIELD MORE HITS IN THE NEAR FUTURE. AS FOR MANY COMPLEX DISEASES, IT IS NOW APPARENT THAT EPIGENETIC EFFECTS ARE ALSO IMPORTANT MEDIATORS OF DISEASE BIOLOGY, WITH DNA METHYLATION, HISTONE MODIFICATIONS AND NON-CODING RNAS ALL HAVING A ROLE. AT PRESENT, MUCH OF THE EPIGENETIC FOCUS HAS BEEN ON CARTILAGE, THE TISSUE AT THE CENTER OF THE OA DISEASE PROCESS. IF WE ARE TO GET CLOSE TO A QUALITATIVE AND QUANTITATIVE UNDERSTANDING OF THE IMPACT OF EPIGENETICS ON OA, THEN IN FUTURE THE OTHER TISSUES OF THE JOINT WILL ALSO NEED TO BE INVESTIGATED. ONE OF THE MORE EXCITING INSIGHTS TO HAVE EMERGED RECENTLY IS THE FACT THAT EPIGENETIC EFFECTS CAN IMPACT ON OA GENETIC EFFECTS AND THIS MAY BE A PARTICULARLY FRUITFUL AVENUE FOR INTEGRATING BOTH AS WE MOVE TOWARD A CLEARER UNDERSTANDING OF THE PATHOPHYSIOLOGY OF THIS INTRIGUING DISEASE. 2012 5 6204 36 THE INFLUENCE OF EPIGENETICS AND INFLAMMATION ON CARDIOMETABOLIC RISKS. CARDIOMETABOLIC DISEASES INCLUDE METABOLIC SYNDROME, OBESITY, TYPE 2 DIABETES MELLITUS, AND HYPERTENSION. EPIGENETIC MODIFICATIONS PARTICIPATE IN CARDIOMETABOLIC DISEASES THROUGH SEVERAL PATHWAYS, INCLUDING INFLAMMATION, VASCULAR DYSFUNCTION, AND INSULIN RESISTANCE. EPIGENETIC MODIFICATIONS, WHICH ENCOMPASS ALTERATIONS TO GENE EXPRESSION WITHOUT MUTATING THE DNA SEQUENCE, HAVE GAINED MUCH ATTENTION IN RECENT YEARS, SINCE THEY HAVE BEEN CORRELATED WITH CARDIOMETABOLIC DISEASES AND MAY BE TARGETED FOR THERAPEUTIC INTERVENTIONS. EPIGENETIC MODIFICATIONS ARE GREATLY INFLUENCED BY ENVIRONMENTAL FACTORS, SUCH AS DIET, PHYSICAL ACTIVITY, CIGARETTE SMOKING, AND POLLUTION. SOME MODIFICATIONS ARE HERITABLE, INDICATING THAT THE BIOLOGICAL EXPRESSION OF EPIGENETIC ALTERATIONS MAY BE OBSERVED ACROSS GENERATIONS. MOREOVER, MANY PATIENTS WITH CARDIOMETABOLIC DISEASES PRESENT WITH CHRONIC INFLAMMATION, WHICH CAN BE INFLUENCED BY ENVIRONMENTAL AND GENETIC FACTORS. THE INFLAMMATORY ENVIRONMENT WORSENS THE PROGNOSIS OF CARDIOMETABOLIC DISEASES AND FURTHER INDUCES EPIGENETIC MODIFICATIONS, PREDISPOSING PATIENTS TO THE DEVELOPMENT OF OTHER METABOLISM-ASSOCIATED DISEASES AND COMPLICATIONS. A DEEPER UNDERSTANDING OF INFLAMMATORY PROCESSES AND EPIGENETIC MODIFICATIONS IN CARDIOMETABOLIC DISEASES IS NECESSARY TO IMPROVE OUR DIAGNOSTIC CAPABILITIES, PERSONALIZED MEDICINE APPROACHES, AND THE DEVELOPMENT OF TARGETED THERAPEUTIC INTERVENTIONS. FURTHER UNDERSTANDING MAY ALSO ASSIST IN PREDICTING DISEASE OUTCOMES, ESPECIALLY IN CHILDREN AND YOUNG ADULTS. THIS REVIEW DESCRIBES EPIGENETIC MODIFICATIONS AND INFLAMMATORY PROCESSES UNDERLYING CARDIOMETABOLIC DISEASES, AND FURTHER DISCUSSES ADVANCES IN THE RESEARCH FIELD WITH A FOCUS ON SPECIFIC POINTS FOR INTERVENTIONAL THERAPY. 2023 6 5670 31 SHARED (EPI)GENOMIC BACKGROUND CONNECTING NEURODEGENERATIVE DISEASES AND TYPE 2 DIABETES. THE PROGRESSIVE AGING OF POPULATIONS HAS RESULTED IN AN INCREASED PREVALENCE OF CHRONIC PATHOLOGIES, ESPECIALLY OF METABOLIC, NEURODEGENERATIVE AND MOVEMENT DISORDERS. IN PARTICULAR, TYPE 2 DIABETES (T2D), ALZHEIMER'S DISEASE (AD) AND PARKINSON'S DISEASE (PD) ARE AMONG THE MOST PREVALENT AGE-RELATED, MULTIFACTORIAL PATHOLOGIES THAT DESERVE PARTICULAR ATTENTION, GIVEN THEIR DRAMATIC IMPACT ON PATIENT QUALITY OF LIFE, THEIR ECONOMIC AND SOCIAL BURDEN AS WELL THE ETIOPATHOGENETIC MECHANISMS, WHICH MAY OVERLAP IN SOME CASES. INDEED, THE EXISTENCE OF COMMON TRIGGERING FACTORS REFLECTS THE CONTRIBUTION OF MUTUAL GENETIC, EPIGENETIC AND ENVIRONMENTAL FEATURES IN THE ETIOPATHOGENETIC MECHANISMS UNDERLYING T2D AND AD/PD. ON THIS SUBJECT, THIS REVIEW WILL SUMMARIZE THE SHARED (EPI)GENOMIC FEATURES THAT CHARACTERIZE THESE COMPLEX PATHOLOGIES. IN PARTICULAR, GENETIC VARIANTS AND GENE EXPRESSION PROFILES ASSOCIATED WITH T2D AND AD/PD WILL BE DISCUSSED AS POSSIBLE CONTRIBUTORS TO DETERMINE THE SUSCEPTIBILITY AND PROGRESSION TO THESE DISORDERS. MOREOVER, POTENTIAL SHARED EPIGENETIC MODIFICATIONS AND FACTORS AMONG T2D, AD AND PD WILL ALSO BE ILLUSTRATED. OVERALL, THIS REVIEW SHOWS THAT FINDINGS FROM GENOMIC STUDIES STILL DESERVES FURTHER RESEARCH TO EVALUATE AND IDENTIFY GENETIC FACTORS THAT DIRECTLY CONTRIBUTE TO THE SHARED ETIOPATHOGENESIS. MOREOVER, A COMMON EPIGENETIC BACKGROUND STILL NEEDS TO BE INVESTIGATED AND CHARACTERIZED. THE EVIDENCES DISCUSSED IN THIS REVIEW UNDERLINE THE IMPORTANCE OF INTEGRATING LARGE-SCALE (EPI)GENOMIC DATA WITH ADDITIONAL MOLECULAR INFORMATION AND CLINICAL AND SOCIAL BACKGROUND IN ORDER TO FINELY DISSECT THE COMPLEX ETIOPATHOGENIC NETWORKS THAT BUILD UP THE "DISEASE INTERACTOME" CHARACTERIZING T2D, AD AND PD. 2020 7 2651 33 EPIGENOMICS AND TRANSCRIPTOMICS IN THE PREDICTION AND DIAGNOSIS OF CHILDHOOD ASTHMA: ARE WE THERE YET? ASTHMA IS THE MOST COMMON NON-COMMUNICABLE CHRONIC DISEASE OF CHILDHOOD. DESPITE ITS HIGH PREVALENCE, TO DATE WE LACK METHODS THAT ARE BOTH EFFICIENT AND ACCURATE IN DIAGNOSING ASTHMA. MOST TRADITIONAL APPROACHES HAVE BEEN BASED ON GARNERING CLINICAL EVIDENCE, SUCH AS RISK FACTORS AND EXPOSURES. GIVEN THE HIGH HERITABILITY OF ASTHMA, MORE RECENT APPROACHES HAVE LOOKED AT GENETIC POLYMORPHISMS AS POTENTIAL "RISK FACTORS." HOWEVER, GENETIC VARIANTS EXPLAIN ONLY A SMALL PROPORTION OF ASTHMA RISK, AND HAVE BEEN LESS THAN OPTIMAL AT PREDICTING RISK FOR INDIVIDUAL SUBJECTS. EPIGENOMIC STUDIES OFFER SIGNIFICANT ADVANTAGES OVER PREVIOUS APPROACHES. EPIGENETIC REGULATION IS HIGHLY TISSUE-SPECIFIC, AND CAN INDUCE BOTH SHORT- AND LONG-TERM CHANGES IN GENE EXPRESSION. SUCH CHANGES CAN START IN UTERO, CAN VARY THROUGHOUT THE LIFE SPAN, AND IN SOME INSTANCES CAN BE PASSED ON FROM ONE GENERATION TO ANOTHER. MOST IMPORTANTLY, THE EPIGENOME CAN BE MODIFIED BY ENVIRONMENTAL FACTORS AND EXPOSURES, AND THUS EPIGENETIC AND TRANSCRIPTOMIC PROFILING MAY YIELD THE MOST ACCURATE RISK ESTIMATES FOR A GIVEN PATIENT BY INCORPORATING ENVIRONMENTAL (AND TREATMENT) EFFECTS THROUGHOUT THE LIFESPAN. HERE WE WILL REVIEW THE MOST RECENT ADVANCES IN THE USE OF EPIGENETIC AND TRANSCRIPTOMIC ANALYSIS FOR THE EARLY DIAGNOSIS OF ASTHMA AND ATOPY, AS WELL AS CHALLENGES AND FUTURE DIRECTIONS IN THE FIELD AS IT MOVES FORWARD. WE WILL PARTICULARLY FOCUS ON DNA METHYLATION, THE MOST STUDIED MECHANISM OF EPIGENETIC REGULATION. 2019 8 1935 28 ENVIRONMENTAL RISK FACTORS AND EPIGENETIC ALTERNATIONS IN PSORIASIS. INTRODUCTION AND OBJECTIVE: PSORIASIS ISA QUITE COMMON, CHRONIC AND IMMUNE-MEDIATED SKIN DISORDER. THE PREVALENCE OF PSORIASIS DIFFERS IN VARIOUS COUNTRIES, BUT IT IS SAID TO AFFECT 2% OF THE WORLD'S POPULATION IN GENERAL. PSORIASIS HAS MANY DIFFERENT CLINICAL FEATURES BUT ALL LESIONS HAVE THE SAME CHARACTERISTIC: ERYTHEMA, THICKENING AND SCALE, ALTHOUGH OTHER CLINICAL FEATURES ARE ALSO CONNECTED, SUCH AS PSORIATIC ARTHRITIS, OBESITY AND METABOLIC SYNDROME. ALL OF THESE MAY LEAD TO CONDITIONS IMPAIRING THE QUALITY OF LIFE. THIS REVIEW IS AN ATTEMPT TO SUMMARIZE RECENT DATA REGARDING ENVIRONMENTAL FACTORS, TOGETHER WITH EPIGENETIC MARKERS AND PROCESSES PLAYING AN IMPORTANT ROLE IN PSORIASIS. STATE OF KNOWLEDGE: MANY DIFFERENT ENVIRONMENTAL FACTORS PLAY A ROLE IN GENETICALLY PREDISPOSED PATIENTS. THIS IS CAUSES EPIGENETIC ALTERNATIONS WHICH MAY BE A LINKING PART IN THE WHOLE PROCESS. MANY STUDIES HAVE INDICATED A CONNECTION BETWEEN PSORIASIS AND VARIOUS GENES AND ANTIGENS. THE PRESENCE OF HLA-CW6 IS COMMON AS WELL A STRONG LINK BETWEEN ITS PRESENCE AND THE ONSET OF PSORIASIS BEING OBSERVED. THE MAIN ALTERNATIONS ARE DNA METHYLATION, HISTONE'S MODIFICATIONS AND THE ROLE OF MICRORNA. EXCESSIVE REACTION IS USUALLY NOT PRESENT WITHOUT A TRIGGERING FACTOR. ENVIRONMENTAL FACTORS ARE MOSTLY RATED, SUCH AS DRUGS, LIFE STYLE AND HABITS (SMOKING, ALCOHOL), DIET, PHYSICAL TRAUMA (SKIN INJURY PROVOKING KOEBNER PHENOMENON), STRESS, MICROORGANISM AND INFECTIONS. CONCLUSIONS: THE CORRELATION BETWEEN PATHOGENESIS OF PSORIASIS AND ENVIRONMENTAL RISK FACTORS, TOGETHER WITH EPIGENETIC ALTERNATIONS STILL REQUIRE MORE INVESTIGATION. EDUCATION ABOUT DIET HABITS, NUTRITION, WEIGHT LOSS AND HEALTHY LIFESTYLE SEEMS TO BE IMPORTANT DURING THE TREATMENT OF PSORIASIS. 2020 9 2570 26 EPIGENETICS OF CHRONIC INFLAMMATORY DISEASES. CHRONIC, NONCOMMUNICABLE, AND INFLAMMATION-ASSOCIATED DISEASES REMAIN THE LARGEST CAUSE OF MORBIDITY AND MORTALITY GLOBALLY AND WITHIN THE UNITED STATES. THIS IS MAINLY DUE TO OUR LIMITED UNDERSTANDING OF THE MOLECULAR MECHANISMS THAT UNDERLIE THESE COMPLEX PATHOLOGIES. THE AVAILABLE EVIDENCE INDICATES THAT STUDIES OF EPIGENETICS (TRADITIONALLY DEFINED AS THE HERITABLE CHANGES TO GENE EXPRESSION THAT ARE INDEPENDENT OF CHANGES TO DNA) ARE SIGNIFICANTLY ADVANCING OUR KNOWLEDGE OF THESE INFLAMMATORY CONDITIONS. THIS REVIEW WILL FOCUS ON EPIGENETIC STUDIES OF THREE DISEASES, THAT ARE AMONG THE MOST BURDENSOME GLOBALLY: CARDIOVASCULAR DISEASE, THE NUMBER ONE CAUSE OF DEATHS WORLDWIDE, TYPE 2 DIABETES AND, ALZHEIMER'S DISEASE. THE CURRENT STATUS OF EPIGENETIC RESEARCH, INCLUDING THE ABILITY TO PREDICT DISEASE RISK, AND KEY PATHOPHYSIOLOGICAL DEFECTS ARE DISCUSSED. THE SIGNIFICANCE OF DEFINING THE CONTRIBUTION OF EPIGENETIC DEFECTS TO NONRESOLVING INFLAMMATION AND AGING, EACH ASSOCIATED WITH THESE DISEASES, IS HIGHLIGHTED, AS THESE ARE LIKELY TO PROVIDE NEW INSIGHTS INTO INFLAMMATORY DISEASE PATHOGENESIS. 2019 10 2586 30 EPIGENETICS OF PAIN MEDIATORS. PURPOSE OF REVIEW: THE FIELD OF EPIGENETICS CONTINUES ITS INFLUENTIAL RISE AS A MEANS TO BETTER UNDERSTAND AN ORGANISM'S UNIQUE DEVELOPMENTAL IDENTITY OVER A LIFESPAN. WHEREAS A GENOME IS CONSTANT AND UNCHANGING, AN EPIGENOME IS DYNAMIC AND ALTERABLE. EPIGENETIC CHANGES ARE IN RESPONSE TO INNUMERABLE INTERNAL AND EXTERNAL INFLUENCES INCLUDING ENVIRONMENTAL CHANGES SUCH AS DIET, EXERCISE, DISEASE, TOXINS, AND STRESS. EPIGENETICS IS OF PARTICULAR INTEREST IN THE MEDICAL RESEARCH COMMUNITY BOTH FOR THE POTENTIAL TO CAUSE DISEASE AND AS A TARGET FOR THERAPEUTIC INTERVENTIONS. THIS ARTICLE PROVIDES A SUCCINCT EXPLANATION OF THE POTENTIAL FOR EPIGENETICS TO INFLUENCE THE UNDERSTANDING OF PAIN AS WELL AS A REVIEW OF RELEVANT RESEARCH ON THE TOPIC. RECENT FINDINGS: STUDIES ON EPIGENETICS AND PAIN REMAIN LARGELY PRECLINICAL AND INVESTIGATE THE THEORETICAL ABILITY OF EPIGENETICS TO ALTER THE NOCICEPTIVE PATHWAYS BOTH IN THE PERIPHERY AND CENTRALLY. SIGNIFICANT EVIDENCE NOW EXISTS FOR THE ABILITY OF EPIGENETICS TO MODIFY BROADLY CATEGORIZED PAIN TYPES, INCLUDING INFLAMMATORY, NEUROPATHIC, VISCERAL, AND CANCER RELATED. SUMMARY: BOTH PATIENTS AND PROVIDERS RECOGNIZE THAT NOVEL MEDICATIONS FOR THE TREATMENT OF BOTH ACUTE AND CHRONIC PAIN CONDITIONS ARE SORELY NEEDED. THE UNDERSTANDING OF EPIGENETICS AND ITS INFLUENCE ON NOCICEPTION REMAINS IN RELATIVE INFANCY BUT EARLY EVIDENCE IS STRONG FOR POTENTIAL THERAPEUTIC BENEFITS TO TREAT THESE CONDITIONS. 2018 11 2027 33 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 12 3653 20 INDIVIDUAL EPIGENETIC VARIATION: WHEN, WHY, AND SO WHAT? EPIGENETICS PROVIDES A POTENTIAL EXPLANATION FOR HOW ENVIRONMENTAL FACTORS MODIFY THE RISK FOR COMMON DISEASES AMONG INDIVIDUALS. INTERINDIVIDUAL VARIATION IN DNA METHYLATION AND EPIGENETIC REGULATION HAS BEEN REPORTED AT SPECIFIC GENOMIC REGIONS INCLUDING TRANSPOSABLE ELEMENTS, GENOMICALLY IMPRINTED GENES AND THE 'INACTIVE' X CHROMOSOMES IN FEMALES. WE CURRENTLY HAVE A VERY POOR UNDERSTANDING OF THE FACTORS THAT CONTRIBUTE TO INTERINDIVIDUAL EPIGENETIC VARIATION. IN PARTICULAR, IT IS IMPORTANT TO UNDERSTAND WHEN DURING THE LIFE CYCLE EPIGENETIC VARIATION ARISES, WHY EPIGENETIC REGULATION VARIES AMONG INDIVIDUALS, AND WHETHER EPIGENETIC INTERINDIVIDUALITY AFFECTS SUSCEPTIBILITY TO DIET-RELATED CHRONIC DISEASE. IN THIS REVIEW WE WILL SUMMARIZE CURRENT PROGRESS TOWARD ANSWERING THESE QUESTIONS. 2008 13 3016 31 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 14 931 28 CHRONIC KIDNEY DISEASE IN CHILDREN AND THE ROLE OF EPIGENETICS: FUTURE THERAPEUTIC TRAJECTORIES. GLOBAL DIFFERENCES IN THE OBSERVED CAUSES OF CHRONIC KIDNEY DISEASE (CKD) IN CHILDREN ARE WELL DOCUMENTED AND ARE ATTRIBUTED TO DISSIMILARITIES IN CLIME, RACE, HEREDITARY, AND ANCESTRY. THUS, FAMILIAL CLUSTERING AND DISPARITIES IN CKD PREVALENCE RATES ACROSS ETHNIC AND RACIAL GROUPS INDICATE THAT THE PROGRESSION OF RENAL DISEASE HAS A STRONG GENETIC COMPONENT. MAMMALIAN STUDIES HAVE DEMONSTRATED A FEASIBLE NEXUS BETWEEN NUTRITION AND NON-GENETIC EXPOSURE (AROUND THE TIME OF CONCEPTION AND IN EPIGENETIC CHANGES) IN THE EXPRESSION OF MAJOR GENES IDENTIFIED IN RENAL ORGANOGENESIS. THE MAJOR CONSEQUENCE IS A REDUCTION IN THE NUMBER OF NEPHRONS, WITH SUBSEQUENT PREDISPOSITION TO HYPERTENSION AND CKD. IDENTIFYING THESE EPIGENETIC CHANGES IS CRUCIAL (DUE TO THEIR POTENTIALLY REVERSIBLE NATURE), AS THEY MAY SERVE AS FUTURE THERAPEUTIC TARGETS TO PREVENT KIDNEY FIBROSIS AND CKD. DESPITE PROGRESS IN THE FIELD OF EPIGENETICS IN ONCOLOGY, RESEARCH IN OTHER SUBSPECIALTIES OF MEDICINE IS LARGELY EXPERIMENTAL WITH FEW EXISTING STUDIES REGARDING THE CLINICAL IMPLICATION OF EPIGENETICS IN RENAL DISEASE. THERAPEUTIC TRAJECTORIES FOR CKD IN CHILDREN BASED ON THE INFLUENCE OF EPIGENETICS MAY EVENTUALLY REVOLUTIONIZE THE MANAGEMENT OF THIS DISEASE. THE AIM OF THE CURRENT NARRATIVE REVIEW IS TO APPRAISE THE ROLE OF EPIGENETICS IN CKD, AND HIGHLIGHT THE POTENTIAL FUTURE THERAPEUTIC PATHWAYS. 2016 15 2492 23 EPIGENETICS AND CHILDHOOD ASTHMA: CURRENT EVIDENCE AND FUTURE RESEARCH DIRECTIONS. ASTHMA IS THE MOST COMMON CHRONIC DISEASE OF CHILDHOOD, AFFECTING ONE IN EIGHT CHILDREN IN THE USA AND WORLDWIDE. IT IS A COMPLEX DISEASE, INFLUENCED BY BOTH ENVIRONMENTAL EXPOSURES AND GENETIC FACTORS. ALTHOUGH EPIGENETIC MODIFICATIONS (DNA METHYLATION, HISTONE MODIFICATION AND MIRNA) CAN AFFECT TRANSCRIPTIONAL ACTIVITY IN MULTIPLE GENETIC PATHWAYS RELEVANT FOR ASTHMA DEVELOPMENT, VERY LIMITED WORK HAS BEEN CARRIED OUT SO FAR TO EXAMINE THE ROLE OF EPIGENETIC VARIATIONS ON ASTHMA DEVELOPMENT AND MANAGEMENT. THIS REVIEW PROVIDES A BRIEF OVERVIEW OF EPIGENETIC MODIFICATIONS, SUMMARIZES RECENT FINDINGS, AND DISCUSSES SOME OF THE MAJOR METHODOLOGICAL CONCERNS THAT ARE RELEVANT FOR ASTHMA EPIGENETICS. 2012 16 2507 27 EPIGENETICS AND OBESITY: THE DEVIL IS IN THE DETAILS. OBESITY IS A COMPLEX DISEASE WITH MULTIPLE WELL-DEFINED RISK FACTORS. NEVERTHELESS, SUSCEPTIBILITY TO OBESITY AND ITS SEQUELAE WITHIN OBESOGENIC ENVIRONMENTS VARIES GREATLY FROM ONE PERSON TO THE NEXT, SUGGESTING A ROLE FOR GENE X ENVIRONMENT INTERACTIONS IN THE ETIOLOGY OF THE DISORDER. EPIGENETIC REGULATION OF THE HUMAN GENOME PROVIDES A PUTATIVE MECHANISM BY WHICH SPECIFIC ENVIRONMENTAL EXPOSURES CONVEY RISK FOR OBESITY AND OTHER HUMAN DISEASES AND IS ONE POSSIBLE MECHANISM THAT UNDERLIES THE GENE X ENVIRONMENT/TREATMENT INTERACTIONS OBSERVED IN EPIDEMIOLOGICAL STUDIES AND CLINICAL TRIALS. A STUDY PUBLISHED IN BMC MEDICINE THIS MONTH BY WANG ET AL. REPORTS ON AN EXAMINATION OF DNA METHYLATION IN PERIPHERAL BLOOD LEUKOCYTES OF LEAN AND OBESE ADOLESCENTS, COMPARING METHYLATION PATTERNS BETWEEN THE TWO GROUPS. THE AUTHORS IDENTIFIED TWO GENES THAT WERE DIFFERENTIALLY METHYLATED, BOTH OF WHICH HAVE ROLES IN IMMUNE FUNCTION. HERE WE OVERVIEW THE FINDINGS FROM THIS STUDY IN THE CONTEXT OF THOSE EMERGING FROM OTHER RECENT GENETIC AND EPIGENETIC STUDIES, DISCUSS THE STRENGTHS AND WEAKNESSES OF THE STUDY AND SPECULATE ON THE FUTURE OF EPIGENETICS IN CHRONIC DISEASE RESEARCH. 2010 17 1453 19 DISCOVERING HOW ENVIRONMENTAL EXPOSURES ALTER GENES COULD LEAD TO NEW TREATMENTS FOR CHRONIC ILLNESSES. EMERGING RESEARCH DEMONSTRATES THAT DIET, POLLUTION, AND OTHER ENVIRONMENTAL TRIGGERS CAN ALTER BOTH THE FUNCTION AND EXPRESSION OF HUMAN GENES AND LEAD TO A HEIGHTENED DISEASE RISK. THESE ENVIRONMENT-GENE INTERACTIONS CAN CAUSE SO-CALLED EPIGENETIC CHANGES IN GENE EXPRESSION-PATTERNS OF WHICH GENES ARE SWITCHED "ON" OR "OFF"-THAT MAY ACCOUNT FOR THE RISING MORTALITY FROM CHRONIC DISEASES IN INDUSTRIALIZED NATIONS. IN THIS PAPER, WE CALL FOR A NEW TRANSDISCIPLINARY APPROACH TO PUBLIC HEALTH THAT WOULD EXAMINE HOW ENVIRONMENTAL EXPOSURES, BOTH PHYSICAL AND SOCIAL, INFLUENCE GENE EXPRESSION AND A PERSON'S SUSCEPTIBILITY TO CHRONIC DISEASE. THIS INITIATIVE COULD LEAD TO NEW WAYS TO PREVENT AND TREAT SUCH ILLNESSES. 2011 18 396 28 AN UPDATE ON EPIGENETICS AND CHILDHOOD RESPIRATORY DISEASES. EPIGENETIC MECHANISMS, DEFINED AS CHANGES IN PHENOTYPE OR GENE EXPRESSION CAUSED BY MECHANISMS OTHER THAN CHANGES IN THE UNDERLYING DNA SEQUENCE, HAVE BEEN PROPOSED TO CONSTITUTE A LINK BETWEEN GENETIC AND ENVIRONMENTAL FACTORS THAT AFFECT COMPLEX DISEASES. RECENT STUDIES SHOW THAT DNA METHYLATION, ONE OF THE KEY EPIGENETIC MECHANISMS, IS ALTERED IN CHILDREN EXPOSED TO AIR POLLUTANTS AND ENVIRONMENTAL TOBACCO SMOKE EARLY IN LIFE. SEVERAL CANDIDATE GENE STUDIES ON EPIGENETICS HAVE BEEN PUBLISHED TO DATE, BUT IT IS ONLY RECENTLY THAT GLOBAL METHYLATION ANALYSES HAVE BEEN PERFORMED FOR RESPIRATORY DISORDERS SUCH AS ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE. HOWEVER, LARGE-SCALE STUDIES WITH ADEQUATE POWER ARE YET TO BE PRESENTED IN CHILDREN, AND IMPLICATIONS FOR CLINICAL USE REMAIN TO BE EVALUATED. IN THIS REVIEW, WE SUMMARIZE THE RECENT ADVANCES IN EPIGENETICS AND RESPIRATORY DISORDERS IN CHILDREN, WITH A MAIN FOCUS ON METHODOLOGICAL CHALLENGES AND ANALYSES RELATED TO PHENOTYPE AND EXPOSURE USING GLOBAL METHYLATION APPROACHES. 2014 19 2447 30 EPIGENETIC STUDIES IN ALZHEIMER'S DISEASE: CURRENT FINDINGS, CAVEATS, AND CONSIDERATIONS FOR FUTURE STUDIES. ALZHEIMER'S DISEASE (AD) IS A SPORADIC, CHRONIC NEURODEGENERATIVE DISEASE, USUALLY OCCURRING LATE IN LIFE. THE LAST DECADE HAS WITNESSED TREMENDOUS ADVANCES IN OUR UNDERSTANDING ABOUT THE GENETIC BASIS OF AD, BUT A LARGE AMOUNT OF THE VARIANCE IN DISEASE RISK REMAINS TO BE EXPLAINED. EPIGENETIC MECHANISMS, WHICH DEVELOPMENTALLY REGULATE GENE EXPRESSION VIA MODIFICATIONS TO DNA, HISTONE PROTEINS, AND CHROMATIN, HAVE BEEN HYPOTHESIZED TO PLAY A ROLE IN OTHER COMPLEX NEUROBIOLOGICAL DISEASES, AND STUDIES TO IDENTIFY GENOME-WIDE EPIGENETIC CHANGES IN AD ARE CURRENTLY UNDER WAY. HOWEVER, THE SIMPLE BRUTE-FORCE APPROACH THAT HAS BEEN SUCCESSFULLY EMPLOYED IN GENOME-WIDE ASSOCIATION STUDIES IS UNLIKELY TO BE SUCCESSFUL IN EPIGENOME-WIDE ASSOCIATION STUDIES OF NEURODEGENERATION. A MORE ACADEMIC APPROACH TO UNDERSTANDING THE ROLE OF EPIGENETIC VARIATION IN AD IS REQUIRED, WITH CAREFUL CONSIDERATION OF STUDY DESIGN, METHODOLOGICAL APPROACHES, TISSUE-SPECIFICITY, AND CAUSAL INFERENCE. IN THIS ARTICLE, WE REVIEW THE EMPIRICAL LITERATURE SUPPORTING A ROLE FOR EPIGENETIC PROCESSES IN AD, AND DISCUSS IMPORTANT CONSIDERATIONS AND FUTURE DIRECTIONS FOR THIS NEW AND EMERGING FIELD OF RESEARCH. 2013 20 34 30 A CHILD'S NUTRITION AND EPIGENETICS. STUDIES HAVE SHOWN A DRAMATIC INCREASE IN THE INCIDENCE AND THE PREVALENCE OF CHRONIC DISEASES SUCH AS TYPE 2 DIABETES MELLITUS AND CARDIOVASCULAR DISORDERS OVER THE LAST SEVERAL DECADES. ENVIRONMENTAL TRIGGERS AND NUTRITION ARE CONSIDERED MAJOR CONTRIBUTORS TO THIS INCREASE. THE FIRST 1,000 DAYS OF LIFE, WHICH IS THE PERIOD BETWEEN CONCEPTION AND THE FIRST 2 YEARS OF AGE, IS CONSIDERED THE TIME FOR ENVIRONMENTAL FACTORS, SUCH AS NUTRITION, TO EXERT THEIR POSITIVE AND MOST CRUCIAL EFFECTS ON A CHILD'S HEALTH. NUTRIGENOMICS, THE STUDY OF HOW GENES AND FOOD COMPONENTS INTERACT, LOOKS INTO DIET-ALTERING DISEASE DEVELOPMENT BY MODULATING PROCESSES INVOLVED WITH THE ONSET, PROGRESSION, AND SEVERITY OF DISEASE. THESE FACTORS AFFECTING THE DEVELOPMENT OF THESE CHRONIC DISEASES ARE THOUGHT TO BE MEDIATED BY EPIGENETIC MECHANISMS, WHICH ARE HERITABLE AND REVERSIBLE, AND CARRY GENETIC INFORMATION WITHOUT CHANGING THE NUCLEOTIDE SEQUENCE OF THE GENOME AND ARE ALSO MEDIATED BY MATERNAL AND POSTNATAL NUTRITION. 2023