1 1165 134 CONTRIBUTION OF DNA METHYLATION TO THE PATHOGENESIS OF SJOGREN'S SYNDROME: A REVIEW. SJOGREN'S SYNDROME (SS) IS A CHRONIC SYSTEMIC DISEASE CHARACTERISED BY SALIVARY AND LACRIMAL GLAND DYSFUNCTION WITH SEVERE IMPLICATIONS FOR THE WELL-BEING OF BEARING INDIVIDUALS. ALTHOUGH ITS ORIGIN HAS NOT YET BEEN FULLY ELUCIDATED, IT IS KNOWN THAT GENETIC, ENVIRONMENTAL, AND EPIGENETIC FACTORS ARE IMPORTANT CONTRIBUTORS TO THE PATHOGENESIS OF THIS SYNDROME. DNA METHYLATION IS A RELEVANT, WIDELY STUDIED EPIGENETIC FACTOR THAT IS POSSIBLY RELATED TO THE ESTABLISHMENT OF SS. THE AIM OF THE PRESENT STUDY WAS TO PERFORM A SYSTEMATIC REVIEW OF THE LITERATURE TO COMPILE STUDIES ON THE CONTRIBUTION OF DNA METHYLATION TO THE PATHOGENESIS OF SS. A LITERATURE SEARCH WAS PERFORMED IN 4 DATABASES (PUBMED, WEB OF SCIENCE, LILACS, AND SCOPUS) USING PREVIOUSLY SELECTED MEDICAL SUBJECT HEADINGS (MESH) DESCRIPTORS, AND ARTICLE SELECTION CONSIDERED OBSERVATIONAL STUDIES ONLY. AFTER A FULL-TEXT READING OF THE SELECTED ARTICLES, 15 STUDIES WERE IN ACCORDANCE WITH THE ELIGIBILITY CRITERIA FOR DATA EXTRACTION. METHYLATION DETECTION APPROACHES INCLUDED GLOBAL METHYLATION, GENOME-WIDE ASSESSMENT OF DIFFERENTIALLY METHYLATED REGIONS, AND SITE-SPECIFIC METHYLATION. FOURTEEN ARTICLES REPORTED ASSOCIATIONS OF DNA METHYLATION PROFILES IN SS PATIENTS, BOTH GLOBALLY AND IN SEVERAL GENES IN SALIVARY GLANDS AND BLOOD CELLS. THUS, DNA METHYLATION MAY CONTRIBUTE TO THE PATHOGENESIS OF SS. THE FINDINGS REINFORCE THE IMPORTANCE OF EPIGENETIC MARKERS IN THE DYNAMICS OF SS AND MAY DIRECT EFFORTS TOWARD THE DEVELOPMENT OF NEW DIAGNOSTIC AND THERAPEUTIC APPROACHES. 2022 2 1603 51 DNA METHYLATION STUDIES IN SALIVA OF PATIENTS WITH SJOGREN'S SYNDROME. SJOGREN'S SYNDROME (SS) IS A RELATIVELY COMMON SYSTEMIC AUTOIMMUNE DISEASE OF UNKNOWN AETIOLOGY, ALTHOUGH GENETIC, HORMONAL, IMMUNOLOGIC, AND ENVIRONMENTAL FACTORS ARE THOUGHT TO BE INVOLVED IN DISEASE PATHOGENESIS. IT IS ALSO TERMED "AUTOIMMUNE EPITHELITIS", AND AFFLICTS MAINLY THE EPITHELIAL STRUCTURES OF SALIVARY AND LACHRYMAL GLANDS, THROUGH PERIEPITHELIAL LYMPHOCYTIC INFILTRATION RESPONSIBLE FOR THE OCCURRENCE OF DRYNESS SYMPTOMS. SJOGREN'S SYNDROME (SS) IS ALSO CHARACTERISED BY B CELL HYPERACTIVITY AS REFLECTED BY THE PRESENCE OF HYPERGAMMAGLOBULINEMIA AND THE PRODUCTION OF AUTOANTIBODIES, WHICH SEEMS TO BE ASSOCIATED WITH THE PRESENCE OF ECTOPIC GERMINAL CENTRES WITHIN THE INFLAMED MINOR SALIVARY GLANDS. CHRONIC ANTIGENIC STIMULATION MAY LEAD TO EXPANSION OF B CELL AUTOREACTIVE CLONES WITH RHEUMATOID FACTOR ACTIVITY, AND ADDITIONAL MOLECULAR EVENTS MEDIATE MALIGNANT TRANSFORMATION INTO NON-HODGKIN'S LYMPHOMAS OF B CELL ORIGIN. THEREFORE, THE INTERACTION BETWEEN THE IMMUNE CELLS OF THE INFLAMMATORY INFILTRATE AND THE SALIVARY EPITHELIUM SEEMS TO HAVE AN IMPORTANT CONTRIBUTION IN DISEASE PROCESS. RECENT HISTOPATHOLOGIC AND MOLECULAR STUDIES HAVE SHOWN THAT DNA METHYLATION LEVELS OF SS PATIENTS COMPARED TO HEALTHY INDIVIDUALS DIFFER IN EPITHELIAL CELLS OF SALIVARY GLANDS AND PERIPHERAL BLOOD MONONUCLEAR CELLS. IN THE PRESENT STUDY, WE INTEND TO ANALYSE THE EPIGENETIC MODIFICATIONS OF DNA IN THE SALIVA OF SS PATIENTS COMPARED TO HEALTHY CONTROLS. MORE SPECIFICALLY, SALIVARY DNA METHYLATION LEVELS OF SELECTED GENETIC LOCI PREVIOUSLY FOUND TO DIFFER IN OTHER TISSUES, WILL BE COMPARED BETWEEN SS PATIENTS AND HEALTHY CONTROLS. THE STUDY INCLUDES SALIVA COLLECTION FROM SS PATIENTS AND HEALTHY INDIVIDUALS, EXTRACTION OF GENOMIC DNA AND METHYLATION ASSESSMENT. THE EPIGENETIC PROFILE OF EACH GENETIC LOCUS WILL BE CORRELATED WITH SS PATIENTS' CLINICAL CHARACTERISTICS AND THE POSSIBILITY OF GENETIC LOCI WITH DIFFERENTIAL DIFFERENCES IN METHYLATION TO BE USED AS POTENTIAL DIAGNOSTIC BIOMARKERS WILL BE EXPLORED. THE CURRENT STUDY IS ANTICIPATED TO REVEAL POTENTIAL BIOMARKERS FOR DIAGNOSTIC AND THERAPEUTIC PURPOSES, OFFERING THE ADVANTAGE TO UTILISE THE EASILY COLLECTED AND HANDLED SALIVA AS THE MAIN BIOLOGIC MATERIAL. 2021 3 6050 41 THE CONTRIBUTION OF EPIGENETICS IN SJOGREN'S SYNDROME. SJOGREN'S SYNDROME (SS) IS A CHRONIC AUTOIMMUNE EPITHELITIS THAT COMBINES EXOCRINE GLAND DYSFUNCTIONS AND LYMPHOCYTIC INFILTRATIONS. WHILE THE PATHOGENESIS OF SS REMAINS UNCLEAR, ITS ETIOLOGY IS MULTIFUNCTIONAL AND INCLUDES A COMBINATION OF GENETIC PREDISPOSITIONS, ENVIRONMENTAL FACTORS, AND EPIGENETIC FACTORS. RECENTLY, INTEREST HAS GROWN IN THE INVOLVEMENT OF EPIGENETICS IN AUTOIMMUNE DISEASES. EPIGENETICS IS DEFINED AS CHANGES IN GENE EXPRESSION, THAT ARE INHERITABLE AND THAT DO NOT ENTAIL CHANGES IN THE DNA SEQUENCE. IN SS, SEVERAL EPIGENETIC MECHANISMS ARE DEFECTIVE INCLUDING DNA DEMETHYLATION THAT PREDOMINATES IN EPITHELIAL CELLS, AN ABNORMAL EXPRESSION OF MICRORNAS, AND ABNORMAL CHROMATIN POSITIONING-ASSOCIATED WITH AUTOANTIBODY PRODUCTION. LAST BUT NOT LEAST, EPIGENETIC MODIFICATIONS ARE REVERSIBLE AS OBSERVED IN MINOR SALIVARY GLANDS FROM SS PATIENTS AFTER B CELL DEPLETION USING RITUXIMAB. THUS EPIGENETIC FINDINGS IN SS OPEN NEW PERSPECTIVES FOR THERAPEUTIC APPROACHES AS WELL AS THE POSSIBLE IDENTIFICATION OF NEW BIOMARKERS. 2014 4 4268 40 MICROBIAL AGENTS AS PUTATIVE INDUCERS OF B CELL LYMPHOMA IN SJOGREN'S SYNDROME THROUGH AN IMPAIRED EPIGENETIC CONTROL: THE STATE-OF-THE-ART. INTRODUCTION: UNDERSTANDING THE MECHANISMS UNDERLYING THE PATHOGENESIS OF SJOGREN'S SYNDROME (SS) IS CRUCIALLY IMPORTANT IN ORDER TO BE ABLE TO DISCRIMINATE THE STEPS THAT LEAD TO B CELL TRANSFORMATION AND PROMPTLY IDENTIFY THE PATIENTS AT RISK OF LYMPHOMAGENESIS. THE AIM OF THIS NARRATIVE REVIEW IS TO DESCRIBE THE EVIDENCE CONCERNING THE ROLE THAT INFECTIONS OR DYSBIOSIS PLAYS IN THE EPIGENETIC CONTROL OF GENE EXPRESSION IN SS PATIENTS AND THEIR POSSIBLE INVOLVEMENT IN B CELL LYMPHOMAGENESIS. MATERIALS AND METHODS: WE SEARCHED THE PUBMED AND GOOGLE SCHOLAR DATABASES AND SELECTED A TOTAL OF 92 ARTICLES PUBLISHED DURING THE LAST 25 YEARS THAT DESCRIBE EXPERIMENTAL AND CLINICAL STUDIES OF THE POTENTIAL ASSOCIATIONS OF MICROBIOTA AND EPIGENETIC ABERRATIONS WITH THE RISK OF B CELL LYMPHOMA IN SS PATIENTS. RESULTS AND DISCUSSION: THE GENETIC BACKGROUND OF SS PATIENTS IS CHARACTERIZED BY THE HYPEREXPRESSION OF GENES THAT ARE MAINLY INVOLVED IN REGULATING THE INNATE AND ADAPTIVE IMMUNE RESPONSES AND ONCOGENESIS. IN ADDITION, SALIVARY GLAND EPITHELIAL CELLS AND LYMPHOCYTES BOTH HAVE AN ALTERED EPIGENETIC BACKGROUND THAT ENHANCES THE ACTIVATION OF PROINFLAMMATORY AND SURVIVAL PATHWAYS. DYSBIOSIS OR CHRONIC LATENT INFECTIONS MAY TUNE THE IMMUNE RESPONSE AND MODIFY THE CELL EPIGENETIC MACHINERY IN SUCH A WAY AS TO GIVE B LYMPHOCYTES AN ACTIVATED OR TRANSFORMED PHENOTYPE. IT IS ALSO WORTH NOTING THAT TRANSPOSABLE INTEGRATED RETROELEMENTS MAY PARTICIPATE IN THE PATHOGENESIS OF SS AND B CELL LYMPHOMAGENESIS BY INDUCING DNA BREAKS, MODULATING CELL GENE EXPRESSION, OR GENERATING ABERRANT TRANSCRIPTS THAT CHRONICALLY STIMULATE THE IMMUNE SYSTEM. CONCLUSIONS: MICROORGANISMS MAY EPIGENETICALLY MODIFY TARGET CELLS AND INDUCE THEIR TRANSCRIPTOME TO GENERATE AN ACTIVATED OR TRANSFORMED PHENOTYPE. THE OCCURRENCE OF LYMPHOMA IN MORE THAN 15% OF SS PATIENTS MAY BE THE END RESULT OF A COMBINATION OF GENETICS, EPIGENETICS, AND DYSBIOSIS OR LATENT INFECTIONS. 2019 5 2515 34 EPIGENETICS AND SJOGREN'S SYNDROME. THERE IS GROWING EVIDENCE THAT EPIGENETICS, THE STUDY OF HERITABLE CHANGES IN GENE EXPRESSION THAT DO NOT INVOLVE MUTATIONS IN THE DNA ITSELF, MAY PLAY AN ESSENTIAL ROLE IN AUTOIMMUNE DISEASES (AID). IN SJOGREN'S SYNDROME (SS), A CHRONIC AID CHARACTERIZED BY AN EPITHELIS OF THE EXOCRINE GLANDS, EPIGENETIC STUDIES HAVE FOCUSED ON THREE MECHANISMS: DNA METHYLATION AND ITS CONSEQUENCES INCLUDING HUMAN ENDOGENOUS RETROVIRUS (HERV) EXPRESSION; MICRORNA EXPRESSION; AND PROTEIN POST-TRANSLATIONAL MODIFICATIONS ASSOCIATED WITH AUTOANTIBODY PRODUCTION. ALTHOUGH IN ITS INFANCY, COMPREHENSION OF THE EPIGENETIC (DYS)REGULATION IN SS MAY HELP US TO UNDERSTAND: WHY SS AFFECTS PREDOMINANTLY MIDDLE-AGED WOMEN; WHY GENETICALLY PREDISPOSED INDIVIDUALS DEVELOP SS BUT NOT OTHERS; WHY FLARE-UPS OCCUR; WHY TREATMENT RESPONSES DIFFER BETWEEN PATIENTS; AND WHY SOME PATIENTS DEVELOP LYMPHOMA. FROM THESE STUDIES WILL ARISE A BETTER COMPREHENSION OF THE PATHOPHYSIOLOGY OF SS AS WELL AS DEVELOPMENT OF NEW DIAGNOSTIC AND PROGNOSTIC BIOMARKERS, AND NOVEL THERAPEUTICS FOR PREVENTION AND PERHAPS EARLY INTERVENTION. 2012 6 6458 41 TIME COURSE OF DNA METHYLATION IN PAIN CONDITIONS: FROM EXPERIMENTAL MODELS TO HUMANS. BACKGROUND AND OBJECTIVE: THROUGHOUT THE LAST DECADE, RESEARCH HAS UNCOVERED ASSOCIATIONS BETWEEN PAIN AND EPIGENETIC ALTERATIONS CAUSED BY ENVIRONMENTAL FACTORS. SPECIFICALLY, STUDIES HAVE DEMONSTRATED CORRELATIONS BETWEEN PAIN CONDITIONS AND ALTERED DNA METHYLATION PATTERNS. THUS, DNA METHYLATION HAS BEEN REVEALED AS A POSSIBLE MODULATOR OR CONTRIBUTOR TO PAIN CONDITIONS, PROVIDING A POTENTIAL THERAPEUTIC TARGET FOR TREATMENT BY DNA METHYLATION MODIFICATION. TO DEVELOP SUCH TREATMENTS, IT IS NECESSARY TO CLARIFY A WIDE NUMBER OF ASPECTS ON HOW DNA METHYLATION AFFECTS PAIN PERCEPTION; FIRST AND FOREMOST, THE TEMPORAL DYNAMICS. THE OBJECTIVE OF THE PRESENT REVIEW IS TO PROVIDE AN OVERVIEW OF CURRENT KNOWLEDGE ON TEMPORAL DYNAMICS OF DNA METHYLATION IN RESPONSE TO PAIN, AND TO INVESTIGATE IF A TIMEFRAME CAN BE ESTABLISHED BASED ON THE DATA OF CURRENTLY PUBLISHED STUDIES. DATABASES AND DATA TREATMENT: PUBMED, MEDLINE, GOOGLE SCHOLAR AND EMBASE WERE SEARCHED COMPREHENSIVELY FOR STUDIES OF DNA METHYLATION IN NEUROPATHIC, INFLAMMATORY AND ALTERNATIVE ANIMAL PAIN MODELS, AND IN CHRONIC PAIN PATIENTS INCLUDING COMPLEX REGIONAL PAIN SYNDROME, CHRONIC POSTSURGICAL PAIN, CHRONIC WIDESPREAD PAIN, FIBROMYALGIA AND CROHN'S DISEASE. RESULTS: WE IDENTIFIED 34 ARTICLES HIGHLIGHTING VARIATIONS IN TEMPORAL DYNAMICS OF DNA METHYLATION ACROSS SPECIES AND BETWEEN DIFFERENT TYPES OF PAIN. THESE STUDIES REPRESENT A STARTING POINT TO UNCOVER NEW INSIGHTS IN THE DNA METHYLATION TIME COURSE IN PAIN. CONCLUSIONS: NO TIMEFRAME CAN CURRENTLY BE MADE FOR THE DNA METHYLATION RESPONSE TO PAIN IN ANY OF THE REVIEWED CONDITIONS, HIGHLIGHTING AN IMPORTANT FOCUS AREA FOR FUTURE RESEARCH. 2021 7 6316 41 THE RELEVANCE OF DNA METHYLATION AND HISTONE MODIFICATION IN PERIODONTITIS: A SCOPING REVIEW. BACKGROUND: PERIODONTITIS IS A CHRONIC INFLAMMATORY DISEASE INVOLVING AN INTERPLAY BETWEEN BACTERIA, INFLAMMATION, HOST RESPONSE GENES, AND ENVIRONMENTAL FACTORS. THE MANIFESTATION OF EPIGENETIC FACTORS DURING PERIODONTITIS PATHOGENESIS AND PERIODONTAL INFLAMMATION IS STILL NOT WELL UNDERSTOOD, WITH LIMITED REVIEWS ON HISTONE MODIFICATION WITH PERIODONTITIS MANAGEMENT. THIS SCOPING REVIEW AIMS TO EVALUATE CURRENT EVIDENCE OF GLOBAL AND SPECIFIC DNA METHYLATION AND HISTONE MODIFICATION IN PERIODONTITIS AND DISCUSS THE GAPS AND IMPLICATIONS FOR FUTURE RESEARCH AND CLINICAL PRACTICE. METHODS: A SCOPING LITERATURE SEARCH OF THREE ELECTRONIC DATABASES WAS PERFORMED IN SCOPUS, MEDLINE (PUBMED) AND EMBASE. AS EPIGENETICS IN PERIODONTITIS IS AN EMERGING RESEARCH FIELD, A SCOPING REVIEW WAS CONDUCTED TO IDENTIFY THE EXTENT OF STUDIES AVAILABLE AND DESCRIBE THE OVERALL CONTEXT AND APPLICABILITY OF THESE RESULTS. RESULTS: OVERALL, 30 STUDIES WERE EVALUATED, AND THE FINDINGS CONFIRMED THAT EPIGENETIC CHANGES IN PERIODONTITIS COMPRISE SPECIFIC MODIFICATIONS TO DNA METHYLATION PATTERNS AND HISTONE PROTEINS MODIFICATION, WHICH CAN EITHER DAMPEN OR PROMOTE THE INFLAMMATORY RESPONSE TO BACTERIAL CHALLENGE. CONCLUSIONS: THE PLASTICITY OF EPIGENETIC MODIFICATIONS HAS IMPLICATIONS FOR THE FUTURE DEVELOPMENT OF TARGETED EPI-DRUGS AND DIAGNOSTIC TOOLS IN PERIODONTITIS. SUCH ADVANCES COULD BE INVALUABLE FOR THE EARLY DETECTION AND MONITORING OF SUSCEPTIBLE INDIVIDUALS. 2022 8 6159 47 THE GENETICS AND EPIGENETICS OF FATIGUE. FATIGUE IS A COMMON SYMPTOM AND INCLUDES BOTH PHYSICAL AND MENTAL COMPONENTS. IT CAN BE ASSOCIATED WITH A VARIETY OF DIFFERENT SYNDROMES AND DISEASES, BUT IN MANY CASES IS NOT ASSOCIATED WITH OTHER COMORBID CONDITIONS. MOST HUMANS HAVE EXPERIENCED ACUTE FATIGUE IN RELATION TO DIFFERENT STRESSORS. ACUTE FATIGUE TYPICALLY DECREASES AS THE EFFECT OF THE TRIGGERING FACTOR IS REDUCED AND A NORMAL HOMEOSTATIC BALANCE IS RESTORED. FATIGUE THAT PERSISTS FOR 6 MONTHS OR MORE IS TERMED CHRONIC FATIGUE. CHRONIC FATIGUE (CF) IN COMBINATION WITH A MINIMUM OF 4 OF 8 SYMPTOMS AND THE ABSENCE OF DISEASES THAT COULD EXPLAIN THESE SYMPTOMS, CONSTITUTE THE CASE DEFINITION FOR CHRONIC FATIGUE SYNDROME. IN SPITE OF ITS PREVALENCE, THE BIOLOGY OF FATIGUE IS RELATIVELY POORLY UNDERSTOOD AND BIOLOGICAL MARKERS HAVE NOT YET BEEN IDENTIFIED. THIS LITERATURE SEARCH WAS PERFORMED IN PUBMED TO IDENTIFY RESEARCH ON THE GENETICS AND EPIGENETICS OF FATIGUE. PUBLICATIONS WERE INCLUDED IF FATIGUE WAS A MAJOR TOPIC AND THE TOPIC WAS COMBINED WITH GENETIC AND/OR EPIGENETIC MEASUREMENTS IN ADULT HUMANS. A TOTAL OF 40 PUBLICATIONS WERE IDENTIFIED. ALTHOUGH ALTERED FUNCTIONING IN THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS, THE SEROTONERGIC SYSTEM, AND ASSOCIATIONS WITH INFECTIOUS AGENTS HAVE BEEN IDENTIFIED, THE SEARCH FOR GENETIC OR EPIGENETIC MARKERS OF FATIGUE, EITHER IN THE CONTEXT OF CF OR CHRONIC FATIGUE SYNDROME (CFS) HAS BEEN RELATIVELY UNPRODUCTIVE OR, IN THE CASE OF EPIGENETICS, NONEXISTENT. ALTHOUGH SEVERAL STUDIES, BOTH HYPOTHESIS-TESTING AND HYPOTHESIS-GENERATING, HAVE BEEN PERFORMED TO SEARCH FOR BIOMARKERS, THEY HAVE MOSTLY BEEN UNDERPOWERED, RESTRICTED BY THE HETEROGENEITY OF THE PHENOTYPE, OR LIMITED BY AN UNSYSTEMATIC STUDY DESIGN. TO BE ABLE TO CONFIRM THE HYPOTHESIS THAT RISK FOR, OR LEVELS OF, FATIGUE ARE INFLUENCED BY THE GENETIC OR EPIGENETIC BACKGROUND OF AN INDIVIDUAL, STUDIES NEED TO BE BASED ON LARGER SAMPLE SIZES WITH A MORE CLEARLY DEFINED PHENOTYPE. STUDIES NEED TO FOCUS NOT ONLY ON THE INFLUENCE OF A SINGLE ASPECT SUCH AS SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) OR DIFFERENTIAL GENE EXPRESSION ON DISEASE RISK OR STATE, BUT ALSO ON THE SYSTEMS BIOLOGY BEHIND THE DISEASE IN COMBINATION WITH INFORMATION ON ENVIRONMENTAL INFLUENCES AND VALIDATION OF FINDINGS IN FUNCTIONAL STUDIES. 2010 9 2093 43 EPIGENETIC EFFECTS FOLLOWING ACUTE AND CHRONIC EXERCISE IN CARDIOVASCULAR DISEASE: A SYSTEMATIC REVIEW. INTRODUCTION: ACUTE EXERCISE AND EXERCISE TRAINING MAY CONFER EPIGENETIC MODIFICATIONS IN HEALTHY SUBJECTS. EPIGENETIC EFFECTS AFTER EXERCISE HAVE BEEN SHOWED IN PATIENTS WITH CARDIOVASCULAR DISEASE. THE AIM OF THIS SYSTEMATIC REVIEW WAS TO SUMMARIZE THE EVIDENCE FROM AVAILABLE CLINICAL TRIALS THAT STUDY EPIGENETIC ADAPTATIONS AFTER EXERCISE IN PATIENTS WITH CARDIOVASCULAR DISEASE. METHODS: THE SEARCH STRATEGY WAS PERFORMED IN PUBMED AND CENTRAL DATABASES ON ARTICLES PUBLISHED UNTIL SEPTEMBER 2020. STUDIES WITH TITLES AND ABSTRACTS RELEVANT TO EXERCISE EPIGENETIC MODIFICATION APPLIED TO CARDIOVASCULAR PATIENTS WERE FULLY EXAMINED. INCLUSION AND EXCLUSION CRITERIA WERE UTILIZED FOR STUDIES SCREENING. QUALITY ASSESSMENT WITH PEDRO SCALE AND EVALUATION BY TWO INDEPENDENT REVIEWERS WAS PERFORMED. RESULTS: OF THE 1714 ARTICLES RETRIEVED, 88 ARTICLES WERE ASSESSED FOR ELIGIBILITY CRITERIA AND 8 ARTICLES MATCHED OUR SEARCH CRITERIA AND FINALLY INCLUDED IN THE SYSTEMATIC ANALYSIS. THE ACUTE EXERCISE EPIGENETIC (MIRNAS) EFFECTS WERE ASSESSED IN THREE STUDIES AND THE CHRONIC EXERCISE TRAINING EFFECTS (MIRNAS AND DNA METHYLATION) IN SIX STUDIES. THE RESULTS HAVE SHOWN THAT THERE IS POSSIBLY AN ACUTE SIGNIFICANT EXERCISE EFFECT ON EPIGENETIC TARGETS WHICH IS MORE EVIDENT AFTER CHRONIC EXERCISE TRAINING. CONCLUSIONS: BY THE PRESENT SYSTEMATIC REVIEW, WE PROVIDE PRELIMINARY EVIDENCE OF BENEFICIAL EPIGENETIC ADAPTATIONS FOLLOWING ACUTE AND CHRONIC EXERCISE IN PATIENTS WITH CARDIOVASCULAR DISEASE. MORE CONTROLLED STUDIES ARE NEEDED TO CONFIRM SUCH EVIDENCE. 2021 10 6790 22 [DNA METHYLATION ANALYSIS IN ENVIRONMENTAL AND OCCUPATIONAL CANCER RESEARCH]. THE PRESENT PAPER REVIEWS RECENT LABORATORY METHODS AND EXPERIMENTAL EVIDENCE CONCERNING EPIGENETIC BIOMARKERS INVOLVED IN CARCINOGENESIS MECHANISMS. WE INTRODUCE DNA METHYLATION AND ITS ROLE IN GENE EXPRESSION CONTROL. DNA METHYLATION ANALYSIS MAY ALLOW TO IDENTIFY EARLY CHANGES LEADING TO CANCER AND OTHER CHRONIC DISEASES. WE DESCRIBE HERE STRATEGIES FOR LABORATORY ANALYSES AND THEIR POSSIBLE APPLICATIONS. WE EXAMINE RESULTS FROM RECENT EXPERIMENTAL STUDIES SUGGESTING THAT THE EFFECTS OF CERTAIN OCCUPATIONAL AGENTS ARE MEDIATED BY ALTERATIONS IN DNA METHYLATION. PLANNING AND CONDUCTING INVESTIGATIONS ON EXPOSED HUMAN SUBJECTS WILL ALLOW TO VERIFY WHETHER DNA METHYLATION CHANGES IDENTIFIED IN ANIMAL AND IN-VITRO STUDIES MAY BE USED AS EARLY-EFFECT AND SUSCEPTIBILITY BIOMARKERS. DNA METHYLATION ANALYSIS HAS THE POTENTIAL FOR FUTURE APPLICATIONS IN RISK ASSESSMENT AND PREVENTION PROGRAMS CONDUCTED ON SUBJECTS EXPOSED TO HUMAN CARCINOGENS. 2005 11 6013 45 THE APPLICATIONS OF DNA METHYLATION AS A BIOMARKER IN KIDNEY TRANSPLANTATION: A SYSTEMATIC REVIEW. BACKGROUND: ALTHOUGH KIDNEY TRANSPLANTATION IMPROVES PATIENT SURVIVAL AND QUALITY OF LIFE, LONG-TERM RESULTS ARE HAMPERED BY BOTH IMMUNE- AND NON-IMMUNE-MEDIATED COMPLICATIONS. CURRENT BIOMARKERS OF POST-TRANSPLANT COMPLICATIONS, SUCH AS ALLOGRAFT REJECTION, CHRONIC RENAL ALLOGRAFT DYSFUNCTION, AND CUTANEOUS SQUAMOUS CELL CARCINOMA, HAVE A SUBOPTIMAL PREDICTIVE VALUE. DNA METHYLATION IS AN EPIGENETIC MODIFICATION THAT DIRECTLY AFFECTS GENE EXPRESSION AND PLAYS AN IMPORTANT ROLE IN PROCESSES SUCH AS ISCHEMIA/REPERFUSION INJURY, FIBROSIS, AND ALLOREACTIVE IMMUNE RESPONSE. NOVEL TECHNIQUES CAN QUICKLY ASSESS THE DNA METHYLATION STATUS OF MULTIPLE LOCI IN DIFFERENT CELL TYPES, ALLOWING A DEEP AND INTERESTING STUDY OF CELLS' ACTIVITY AND FUNCTION. THEREFORE, DNA METHYLATION HAS THE POTENTIAL TO BECOME AN IMPORTANT BIOMARKER FOR PREDICTION AND MONITORING IN KIDNEY TRANSPLANTATION. PURPOSE OF THE STUDY: THE AIM OF THIS STUDY WAS TO EVALUATE THE ROLE OF DNA METHYLATION AS A POTENTIAL BIOMARKER OF GRAFT SURVIVAL AND COMPLICATIONS DEVELOPMENT IN KIDNEY TRANSPLANTATION. MATERIAL AND METHODS: A SYSTEMATIC REVIEW OF SEVERAL DATABASES HAS BEEN CONDUCTED. THE NEWCASTLE-OTTAWA SCALE AND THE JADAD SCALE HAVE BEEN USED TO ASSESS THE RISK OF BIAS FOR OBSERVATIONAL AND RANDOMIZED STUDIES, RESPECTIVELY. RESULTS: TWENTY ARTICLES REPORTING ON DNA METHYLATION AS A BIOMARKER FOR KIDNEY TRANSPLANTATION WERE INCLUDED, ALL USING DNA METHYLATION FOR PREDICTION AND MONITORING. DNA METHYLATION PATTERN ALTERATIONS IN CELLS ISOLATED FROM DIFFERENT TISSUES, SUCH AS KIDNEY BIOPSIES, URINE, AND BLOOD, HAVE BEEN ASSOCIATED WITH ISCHEMIA-REPERFUSION INJURY AND CHRONIC RENAL ALLOGRAFT DYSFUNCTION. THESE ALTERATIONS OCCURRED IN DIFFERENT AND SPECIFIC LOCI. DNA METHYLATION STATUS HAS ALSO PROVED TO BE IMPORTANT FOR IMMUNE RESPONSE MODULATION, HAVING A CRUCIAL ROLE IN REGULATORY T CELL DEFINITION AND ACTIVITY. RESEARCH ALSO FOCUSED ON A BETTER UNDERSTANDING OF THE ROLE OF THIS EPIGENETIC MODIFICATION ASSESSMENT FOR REGULATORY T CELLS ISOLATION AND EXPANSION FOR FUTURE TOLERANCE INDUCTION-ORIENTED THERAPIES. CONCLUSIONS: STUDIES INCLUDED IN THIS REVIEW ARE HETEROGENEOUS IN STUDY DESIGN, BIOLOGICAL SAMPLES, AND OUTCOME. MORE COORDINATED INVESTIGATIONS ARE NEEDED TO AFFIRM DNA METHYLATION AS A CLINICALLY RELEVANT BIOMARKER IMPORTANT FOR PREVENTION, MONITORING, AND INTERVENTION. 2022 12 1998 42 EPIGENETIC AND MIRNA EXPRESSION CHANGES IN PEOPLE WITH PAIN: A SYSTEMATIC REVIEW. ACCUMULATING EVIDENCE SUGGESTS THAT EPIGENETIC MECHANISMS MAY HOLD GREAT POTENTIAL IN THE FIELD OF PAIN. WE SYSTEMATICALLY REVIEWED THE LITERATURE EXPLORING EPIGENETIC MECHANISMS IN PEOPLE WITH PAIN. FOUR DATABASES HAVE BEEN INTERROGATED: MEDLINE, THE COCHRANE CENTRAL REGISTER OF CONTROLLED TRIAL, SCOPUS, AND WEB OF SCIENCE, FOLLOWING PRISMA GUIDELINES IN CONDUCTING STUDY SELECTION AND ASSESSMENT. THIRTY-SEVEN STUDIES WERE INCLUDED. STUDIES EXPLORED EPIGENETICS IN CONDITIONS SUCH AS FIBROMYALGIA, CRPS, NEUROPATHIES, OR OSTEOARTHRITIS. RESEARCH FOCUSSED ON GENOME-WIDE AND GENE-SPECIFIC DNA METHYLATION, AND MIRNA EXPRESSION. BIOINFORMATICS ANALYSES EXPLORING MIRNA-ASSOCIATED MOLECULAR PATHWAYS WERE ALSO PERFORMED. SEVERAL GENES ALREADY KNOWN FOR THEIR ROLE IN PAIN (BDNF, HDAC4, PRKG1, IL-17, TNFRSF13B, ETC.), AND SEVERAL MIRNAS LINKED TO INFLAMMATORY REGULATION, NOCICEPTIVE SIGNALLING AND PROTEIN KINASES FUNCTIONS HAVE BEEN FOUND TO DIFFER SIGNIFICANTLY BETWEEN PEOPLE WITH CHRONIC PAIN AND HEALTHY CONTROLS. ALTHOUGH THE STUDIES INCLUDED WERE CROSS-SECTIONAL IN NATURE, AND NO CONCLUSION ON CAUSAL LINKS BETWEEN EPIGENETIC CHANGES AND PAIN COULD BE DRAWN, WE SUMMARISED THE LARGE AMOUNT OF DATA AVAILABLE IN LITERATURE ON THE TOPIC, HIGHLIGHTING RESULTS THAT HAVE BEEN REPLICATED BY INDEPENDENT INVESTIGATIONS. THE FIELD OF PAIN EPIGENETICS APPEARS VERY EXCITING AND HAS ALL THE POTENTIAL TO LEAD TO REMARKABLE SCIENTIFIC ADVANCES. HOWEVER, HIGH-QUALITY, WELL-POWERED, LONGITUDINAL STUDIES ARE WARRANTED. PERSPECTIVE: THOUGH MORE HIGH-QUALITY RESEARCH IS NEEDED, AVAILABLE RESEARCH EXPLORING EPIGENETIC MECHANISMS OR MIRNAS IN PEOPLE WITH PAIN SHOWS THAT GENES REGULATING SYNAPTIC PLASTICITY AND EXCITABILITY, PROTEIN KINASES, AND ELEMENTS OF THE IMMUNE SYSTEM MIGHT HOLD GREAT POTENTIAL IN UNDERSTANDING THE PATHOPHYSIOLOGY OF DIFFERENT CONDITIONS. 2020 13 1844 43 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 14 666 48 BLOOD-BASED DNA METHYLATION BIOMARKERS FOR TYPE 2 DIABETES: POTENTIAL FOR CLINICAL APPLICATIONS. TYPE 2 DIABETES (T2D) IS A LEADING CAUSE OF DEATH AND DISABILITY WORLDWIDE. IT IS A CHRONIC METABOLIC DISORDER THAT DEVELOPS DUE TO AN INTERPLAY OF GENETIC, LIFESTYLE, AND ENVIRONMENTAL FACTORS. THE BIOLOGICAL ONSET OF THE DISEASE OCCURS LONG BEFORE CLINICAL SYMPTOMS DEVELOP, THUS THE SEARCH FOR EARLY DIAGNOSTIC AND PROGNOSTIC BIOMARKERS, WHICH COULD FACILITATE INTERVENTION STRATEGIES TO PREVENT OR DELAY DISEASE PROGRESSION, HAS INCREASED CONSIDERABLY IN RECENT YEARS. EPIGENETIC MODIFICATIONS REPRESENT IMPORTANT LINKS BETWEEN GENETIC, ENVIRONMENTAL AND LIFESTYLE CUES AND INCREASING EVIDENCE IMPLICATE ALTERED EPIGENETIC MARKS SUCH AS DNA METHYLATION, THE MOST CHARACTERIZED AND WIDELY STUDIED EPIGENETIC MECHANISM, IN THE PATHOGENESIS OF T2D. THIS REVIEW PROVIDES AN UPDATE OF THE CURRENT STATUS OF DNA METHYLATION AS A BIOMARKER FOR T2D. FOUR DATABASES, SCOPUS, PUBMED, COCHRANE CENTRAL, AND GOOGLE SCHOLAR WERE SEARCHED FOR STUDIES INVESTIGATING DNA METHYLATION IN BLOOD. THIRTY-SEVEN STUDIES WERE IDENTIFIED, AND ARE SUMMARIZED WITH RESPECT TO POPULATION CHARACTERISTICS, BIOLOGICAL SOURCE, AND METHOD OF DNA METHYLATION QUANTIFICATION (GLOBAL, CANDIDATE GENE OR GENOME-WIDE). WE HIGHLIGHT THAT DIFFERENTIAL METHYLATION OF THE TCF7L2, KCNQ1, ABCG1, TXNIP, PHOSPHO1, SREBF1, SLC30A8, AND FTO GENES IN BLOOD ARE REPRODUCIBLY ASSOCIATED WITH T2D IN DIFFERENT POPULATION GROUPS. THESE GENES SHOULD BE PRIORITIZED AND REPLICATED IN LONGITUDINAL STUDIES ACROSS MORE POPULATIONS IN FUTURE STUDIES. FINALLY, WE DISCUSS THE LIMITATIONS FACED BY DNA METHYLATION STUDIES, WHICH INCLUDE INCLUDING INTERPATIENT VARIABILITY, CELLULAR HETEROGENEITY, AND LACK OF ACCOUNTING FOR STUDY CONFOUNDERS. THESE LIMITATIONS AND CHALLENGES MUST BE OVERCOME BEFORE THE IMPLEMENTATION OF BLOOD-BASED DNA METHYLATION BIOMARKERS INTO A CLINICAL SETTING. WE EMPHASIZE THE NEED FOR LONGITUDINAL PROSPECTIVE STUDIES TO SUPPORT THE ROBUSTNESS OF THE CURRENT FINDINGS OF THIS REVIEW. 2018 15 1546 30 DNA METHYLATION IN NASAL EPITHELIUM: STRENGTHS AND LIMITATIONS OF AN EMERGENT BIOMARKER FOR CHILDHOOD ASTHMA. ASTHMA IS ONE OF THE MOST WIDESPREAD CHRONIC RESPIRATORY CONDITIONS. THIS DISEASE PRIMARILY DEVELOPS IN CHILDHOOD AND IS INFLUENCED BY DIFFERENT FACTORS, MAINLY GENETICS AND ENVIRONMENTAL FACTORS. DNA METHYLATION IS AN EPIGENETIC MECHANISM WHICH MAY REPRESENT A BRIDGE BETWEEN THESE TWO FACTORS, PROVIDING A TOOL TO COMPREHEND THE INTERACTION BETWEEN GENETICS AND ENVIRONMENT. MOST EPIDEMIOLOGICAL STUDIES IN THIS FIELD HAVE BEEN CONDUCTED USING BLOOD SAMPLES, ALTHOUGH DNA METHYLATION MARKS IN BLOOD MAY NOT BE RELIABLE FOR DRAWING EXHAUSTIVE CONCLUSIONS ABOUT DNA METHYLATION IN THE AIRWAYS. BECAUSE OF THE ROLE OF NASAL EPITHELIUM IN ASTHMA AND THE TISSUE SPECIFICITY OF DNA METHYLATION, STUDYING THE RELATIONSHIP BETWEEN DNA METHYLATION AND CHILDHOOD ASTHMA MIGHT REVEAL CRUCIAL INFORMATION ABOUT THIS WIDESPREAD RESPIRATORY DISEASE. THE PURPOSE OF THIS REVIEW IS TO DESCRIBE CURRENT FINDINGS IN THIS FIELD OF RESEARCH. WE WILL PRESENT A VIEWPOINT OF SELECTED STUDIES, CONSIDER STRENGTHS AND LIMITATIONS, AND PROPOSE FUTURE RESEARCH IN THIS AREA. 2020 16 2507 32 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 2017 36 EPIGENETIC BIOMARKERS IN RHEUMATOLOGY - THE FUTURE? EPIGENETIC CHANGES ARE STABLE MODIFICATIONS OF DNA OR HISTONES THAT PROFOUNDLY ALTER GENE EXPRESSION. THEY CAN BE CHANGED BY ENVIRONMENTAL INFLUENCES AND CAN THEN BE PASSED ON TO DAUGHTER CELLS OR VIA THE GERM LINE TO OFFSPRING. A VARIETY OF CHANGES IN EPIGENETIC MARKS AND IN THE EXPRESSION OF NONCODING RNA HAS BEEN FOUND IN CANCER AS WELL AS IN CHRONIC INFLAMMATORY DISEASES. INTERESTINGLY, IN BOTH DISEASES SIMILAR MECHANISMS AND PATHWAYS ARE AFFECTED ALBEIT OFTEN TO A DIFFERENT EXTENT. DNA METHYLATION IS OFTEN LOST IN REPETITIVE SEQUENCES, WHILE IN PROMOTER REGIONS HYPO- AS WELL AS HYPERMETHYLATION IS FOUND. CHANGES IN MICRORNA LEVELS TYPICALLY AFFECT MICRORNAS THAT ARE CHANGED BY AN INFLAMMATORY ENVIRONMENT, BUT DISEASE SPECIFIC CHANGES HAVE ALSO BEEN FOUND IN THE BLOOD AND VARIOUS CELL TYPES OF PATIENTS WITH RHEUMATOID ARTHRITIS, SYSTEMIC LUPUS ERYTHEMATOSUS AND OTHER RHEUMATIC DISEASES. THEREFORE, CHANGES IN THE EXPRESSION OF MICRORNA IN PARTICULAR, BUT ALSO DEMETHYLATED GENE LOCI, HAVE BEEN PROPOSED AS POTENTIAL BIOMARKERS IN CHRONIC INFLAMMATORY DISEASES AND IN CANCER. POTENTIALLY, THESE CHANGES COULD BE USED FOR EARLY DIAGNOSIS AND ALSO TO PREDICT TREATMENT RESPONSE. UNFORTUNATELY MOST STUDIES IN RHEUMATOLOGY UP TO NOW WERE NOT DESIGNED TO VALIDATE THESE EPIGENETIC CHANGES AS BIOMARKERS. SINCE THE CANCER FIELD IS MUCH MORE ADVANCED IN THE USAGE OF BIOMARKERS FOR DISEASE SUBCLASSIFICATIONS AND SUBSEQUENT THERAPEUTIC DECISIONS, IT IS WORTHWHILE TO TAKE A CLOSER LOOK AT THE BIOMARKERS, METHODS AND PROCEDURES USED IN ONCOLOGY AND TO SEE WHICH OF THESE COULD ALSO BE APPLIED TO PREDICTING DISEASE SEVERITY AND THERAPEUTIC RESPONSE IN RHEUMATIC DISEASES. THIS ARTICLE WILL HIGHLIGHT COMMON EPIGENETIC PATHWAYS ACTIVATED IN CANCER AND VARIOUS RHEUMATIC DISEASES AND SUMMARISE EPIGENETIC CHANGES THAT HAVE THE POTENTIAL TO BECOME BIOMARKERS IN RHEUMATIC DISEASES. 2016 18 3026 35 GENETICS OF BEHCET'S DISEASE: FUNCTIONAL GENETIC ANALYSIS AND ESTIMATING DISEASE HERITABILITY. BEHCET'S DISEASE IS A CHRONIC MULTISYSTEMIC INFLAMMATORY DISORDER CHARACTERIZED BY RECURRENT ORAL AND GENITAL ULCERS. ALTHOUGH ITS ETIOLOGY REMAINS UNCLEAR, IT IS THOUGHT THAT BOTH GENETIC AND ENVIRONMENTAL FACTORS CONTRIBUTE TO THE ONSET AND PROGRESSION OF BEHCET'S DISEASE. HERE, WE PROVIDE AN UPDATED VIEW OF THE GENETIC LANDSCAPE AND ARCHITECTURE OF BEHCET'S DISEASE. LARGE-SCALE GENETIC STUDIES PERFORMED TO DATE REVEALED 21 GENETIC SUSCEPTIBILITY LOCI ASSOCIATED WITH THE DISEASE AT A GWAS LEVEL OF SIGNIFICANCE (P-VALUE = 5 X 10(-8)). WE PERFORMED EPIGENETIC PATTERN ENRICHMENT ANALYSIS IN BEHCET'S DISEASE ASSOCIATED LOCI, PROVIDING NEW INSIGHTS INTO THE MOLECULAR MECHANISMS UNDERLYING ITS PATHOPHYSIOLOGY. OUR DATA SUGGEST THE CRUCIAL INVOLVEMENT OF SEVERAL IMMUNE CELL TYPES, INCLUDING NATURAL KILLER CELLS, MONOCYTES, AND B CELLS IN THE PATHOGENESIS OF THE DISEASE. PATHWAY ENRICHMENT ANALYSIS IDENTIFIED IMPORTANT BIOLOGICAL PROCESSES INVOLVED. USING LARGE-SCALE GENETIC DATA AVAILABLE FROM ~200 IMMUNE-RELATED LOCI (IMMUNOCHIP), WE ESTIMATE BEHCET'S DISEASE HERITABILITY TO BE AT LEAST 16%. WE FURTHER USED THE SAME APPROACH TO ESTIMATE THE HERITABILITY EXPLAINED BY THE KNOWN BEHCET'S DISEASE-ASSOCIATED LOCI, SUGGESTING THAT THEY EXPLAIN ~ 60% OF THE GENETIC COMPONENT UNDERLYING BEHCET'S DISEASE. THESE RESULTS INDICATE A SIGNIFICANT ROLE OF NON-GENETIC FACTORS IN CAUSING BEHCET'S DISEASE AND THAT ADDITIONAL GENETIC VARIATION INFLUENCING THE RISK OF BEHCET'S DISEASE REMAINS TO BE IDENTIFIED. FINALLY, WE CALCULATED A CUMULATIVE GENETIC RISK SCORE ACROSS POPULATIONS REINFORCING THE LINK BETWEEN GEOGRAPHIC VARIATIONS IN DISEASE PREVALENCE WITH ITS GENETIC COMPONENT. 2021 19 1518 32 DNA METHYLATION AS AN EPIGENETIC MECHANISM IN THE DEVELOPMENT OF MULTIPLE SCLEROSIS. THE EPIGENETIC MECHANISMS OF GENE EXPRESSION REGULATION ARE A GROUP OF THE KEY CELLULAR AND MOLECULAR PATHWAYS THAT LEAD TO INHERITED ALTERATIONS IN GENES' ACTIVITY WITHOUT CHANGING THEIR CODING SEQUENCE. DNA METHYLATION AT THE C5 POSITION OF CYTOSINE IN CPG DINUCLEOTIDES IS AMONGST THE CENTRAL EPIGENETIC MECHANISMS. CURRENTLY, THE NUMBER OF STUDIES THAT ARE DEVOTED TO THE IDENTIFICATION OF METHYLATION PATTERNS SPECIFIC TO MULTIPLE SCLEROSIS (MS), A SEVERE CHRONIC AUTOIMMUNE DISEASE OF THE CENTRAL NERVOUS SYSTEM, IS ON A RAPID RISE. HOWEVER, THE ISSUE OF THE CONTRIBUTION OF DNA METHYLATION TO THE DEVELOPMENT OF THE DIFFERENT CLINICAL PHENOTYPES OF THIS HIGHLY HETEROGENEOUS DISEASE HAS ONLY BEGUN TO ATTRACT THE ATTENTION OF RESEARCHERS. THIS REVIEW SUMMARIZES THE DATA ON THE MOLECULAR MECHANISMS UNDERLYING DNA METHYLATION AND THE MS RISK FACTORS THAT CAN AFFECT THE DNA METHYLATION PROFILE AND, THEREBY, MODULATE THE EXPRESSION OF THE GENES INVOLVED IN THE DISEASE'S PATHOGENESIS. THE FOCUS OF OUR ATTENTION IS CENTERED ON THE ANALYSIS OF THE PUBLISHED DATA ON THE DIFFERENTIAL METHYLATION OF DNA FROM VARIOUS BIOLOGICAL SAMPLES OF MS PATIENTS OBTAINED USING BOTH THE CANDIDATE GENE APPROACH AND HIGH-THROUGHPUT METHODS. 2021 20 2213 42 EPIGENETIC MODIFICATIONS AS OUTCOMES OF EXERCISE INTERVENTIONS RELATED TO SPECIFIC METABOLIC ALTERATIONS: A SYSTEMATIC REVIEW. BACKGROUND: CHRONIC DISEASES ARISE AS A CONSEQUENCE OF AN UNHEALTHY LIFESTYLE PRIMARILY CHARACTERIZED BY PHYSICAL INACTIVITY AND UNBALANCED DIETS. REGULAR PHYSICAL ACTIVITY CAN IMPROVE HEALTH, AND THERE IS CONSISTENT EVIDENCE THAT THESE IMPROVEMENTS MAY BE THE RESULT OF EPIGENETIC MODIFICATIONS. OBJECTIVE: TO IDENTIFY EPIGENETIC MODIFICATIONSAS OUTCOMES OF EXERCISE INTERVENTIONS RELATED TO SPECIFIC METABOLIC ALTERATIONS. METHODS: THE PREFERRED REPORTING ITEMS FOR SYSTEMATIC REVIEWS AND META-ANALYSES PROTOCOLS (PRISMA-P) METHODOLOGY FOR MANUSCRIPT RESEARCH AND PREPARATION WAS FOLLOWED USING PUBMED AND EBSCO DATABASES FOR LITERATURE REVIEW. OUT OF 2,638 ARTICLES IDENTIFIED, ONLY 34 ARTICLES MET THE INCLUSION CRITERIA. RESULTS: THE SECTIONS OF THE REVIEW WERE ORGANIZED BY METABOLIC ALTERATIONS IN WHICH STUDIES WERE GROUPED ACCORDING TO HEALTHY, DISEASED, AND TRAINED INDIVIDUALS. RESISTANCE EXERCISE IN HUMANS INDUCED EPIGENETIC CHANGES IN PATHWAYS ASSOCIATED WITH ENERGY METABOLISM AND INSULIN SENSITIVITY, CONTRIBUTING TO HEALTHY SKELETAL MUSCLE. ENDURANCE EXERCISE ALSO CAUSED MODIFICATIONS IN BIOMARKERS ASSOCIATED TO METABOLIC ALTERATIONS THROUGH CHANGES IN DNA METHYLATION AND THE EXPRESSION OF SPECIFIC MIRNAS. HOWEVER, BOTH RESISTANCE AND ENDURANCE EXERCISE ARE NECESSARY TO OBTAIN A BETTER PHYSIOLOGICAL ADAPTATION AND A COMBINATION OF BOTH SEEMS TO BE NEEDED TO PROPERLY TACKLE THE INCREASING PREVALENCE OF NON-COMMUNICABLE PATHOLOGIES. CONCLUSION: GIVEN THE HETEROGENEITY AND COMPLEXITY OF THE EXISTING LITERATURE, IT IS CURRENTLY NOT POSSIBLE TO PROPOSE A SPECIFIC RECOMMENDATION ABOUT THE TYPE, INTENSITY, OR DURATION OF EXERCISE THAT COULD BE BENEFICIAL FOR DIFFERENT SUBSETS OF THE POPULATION (HEALTHY, DISEASED, AND/OR TRAINED). NEVERTHELESS, THIS REVIEW HIGHLIGHTS THE IMPORTANCE OF EXERCISE FOR HEALTH AND SHOWS THE NEED TO PERFORM MORE RESEARCH IN THIS EMERGING AREA TO IDENTIFY EPIGENETIC BIOMARKERS THAT COULD SERVE AS INDICATORS OF EXERCISE ADAPTATIONS. 2019