1 528 122 ASTHMA EPIGENETICS. ASTHMA IS THE MOST COMMON CHRONIC DISEASE OF CHILDHOOD, AND A GROWING BODY OF EVIDENCE INDICATES THAT EPIGENETIC VARIATIONS MAY MEDIATE THE EFFECTS OF ENVIRONMENTAL EXPOSURES ON THE DEVELOPMENT AND NATURAL HISTORY OF ASTHMA. EPIGENETICS IS THE STUDY OF MITOTICALLY OR MEIOTICALLY HERITABLE CHANGES IN GENE EXPRESSION THAT OCCUR WITHOUT DIRECTLY ALTERING THE DNA SEQUENCE. DNA METHYLATION, HISTONE MODIFICATIONS AND MICRORNAS ARE MAJOR EPIGENETIC VARIATIONS IN HUMANS THAT ARE CURRENTLY BEING INVESTIGATED FOR ASTHMA ETIOLOGY AND NATURAL HISTORY. DNA METHYLATION RESULTS FROM ADDITION OF A METHYL GROUP TO THE 5 POSITION OF A CYTOSINE RING AND OCCURS ALMOST EXCLUSIVELY ON A CYTOSINE IN A CPG DINUCLEOTIDE. HISTONE MODIFICATIONS INVOLVE POSTTRANSLATIONAL MODIFICATIONS SUCH AS ACETYLATION, METHYLATION, PHOSPHORYLATION AND UBIQUITINATION ON THE TAILS OF CORE HISTONES. MICRORNAS ARE SHORT ~22 NUCLEOTIDE LONG, NON-CODING, SINGLE-STRANDED RNAS THAT BINDS TO COMPLEMENTARY SEQUENCES IN THE TARGET MRNAS, USUALLY RESULTING IN GENE SILENCING. WHILE MANY STUDIES HAVE DOCUMENTED RELATIONSHIPS OF ENVIRONMENTAL EXPOSURES THAT HAVE BEEN IMPLICATED IN ASTHMA ETIOLOGY WITH EPIGENETIC ALTERATIONS, TO DATE, FEW STUDIES HAVE DIRECTLY LINKED EPIGENETIC VARIATIONS WITH ASTHMA DEVELOPMENT. THERE ARE SEVERAL METHODOLOGICAL CHALLENGES IN STUDYING THE EPIGENETICS OF ASTHMA. IN THIS CHAPTER, THE INFLUENCE OF EPIGENETIC VARIATIONS ON ASTHMA PATHOPHYSIOLOGY, METHODOLOGICAL CONCERNS IN CONDUCTING EPIGENETIC RESEARCH AND FUTURE DIRECTION OF ASTHMA EPIGENETICS RESEARCH ARE DISCUSSED. 2014 2 2330 42 EPIGENETIC REGULATION OF IMMUNE FUNCTION IN ASTHMA. ASTHMA IS A COMMON COMPLEX RESPIRATORY DISEASE CHARACTERIZED BY CHRONIC AIRWAY INFLAMMATION AND PARTIALLY REVERSIBLE AIRFLOW OBSTRUCTION RESULTING FROM GENETIC AND ENVIRONMENTAL DETERMINANTS. BECAUSE EPIGENETIC MARKS INFLUENCE GENE EXPRESSION AND CAN BE MODIFIED BY BOTH ENVIRONMENTAL EXPOSURES AND GENETIC VARIATION, THEY ARE INCREASINGLY RECOGNIZED AS RELEVANT TO THE PATHOGENESIS OF ASTHMA AND MAY BE A KEY LINK BETWEEN ENVIRONMENTAL EXPOSURES AND ASTHMA SUSCEPTIBILITY. UNLIKE CHANGES TO DNA SEQUENCE, EPIGENETIC SIGNATURES ARE DYNAMIC AND REVERSIBLE, CREATING AN OPPORTUNITY FOR NOT ONLY THERAPEUTIC TARGETS BUT MAY SERVE AS BIOMARKERS TO FOLLOW DISEASE COURSE AND IDENTIFY MOLECULAR SUBTYPES IN HETEROGENEOUS DISEASES SUCH AS ASTHMA. IN THIS REVIEW, WE WILL EXAMINE THE RELATIONSHIP BETWEEN ASTHMA AND 3 KEY EPIGENETIC PROCESSES THAT MODIFY GENE EXPRESSION: DNA METHYLATION, MODIFICATION OF HISTONE TAILS, AND NONCODING RNAS. IN ADDITION TO PRESENTING A COMPREHENSIVE ASSESSMENT OF THE EXISTING EPIGENETIC STUDIES FOCUSING ON IMMUNE REGULATION IN ASTHMA, WE WILL DISCUSS FUTURE DIRECTIONS FOR EPIGENETIC INVESTIGATION IN ALLERGIC AIRWAY DISEASE. 2022 3 396 37 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 4 2282 40 EPIGENETIC REGULATION IN EXPOSOME-INDUCED TUMORIGENESIS: EMERGING ROLES OF NCRNAS. ENVIRONMENTAL FACTORS, INCLUDING POLLUTANTS AND LIFESTYLE, CONSTITUTE A SIGNIFICANT ROLE IN SEVERE, CHRONIC PATHOLOGIES WITH AN ESSENTIAL SOCIETAL, ECONOMIC BURDEN. THE MEASUREMENT OF ALL ENVIRONMENTAL EXPOSURES AND ASSESSING THEIR CORRELATION WITH EFFECTS ON INDIVIDUAL HEALTH IS DEFINED AS THE EXPOSOME, WHICH INTERACTS WITH OUR UNIQUE CHARACTERISTICS SUCH AS GENETICS, PHYSIOLOGY, AND EPIGENETICS. EPIGENETICS INVESTIGATES MODIFICATIONS IN THE EXPRESSION OF GENES THAT DO NOT DEPEND ON THE UNDERLYING DNA SEQUENCE. SOME STUDIES HAVE CONFIRMED THAT ENVIRONMENTAL FACTORS MAY PROMOTE DISEASE IN INDIVIDUALS OR SUBSEQUENT PROGENY THROUGH EPIGENETIC ALTERATIONS. VARIATIONS IN THE EPIGENETIC MACHINERY CAUSE A SPECTRUM OF DIFFERENT DISORDERS SINCE THESE MECHANISMS ARE MORE SENSITIVE TO THE ENVIRONMENT THAN THE GENOME, DUE TO THE INHERENT REVERSIBLE NATURE OF THE EPIGENETIC LANDSCAPE. SEVERAL EPIGENETIC MECHANISMS, INCLUDING MODIFICATIONS IN DNA (E.G., METHYLATION), HISTONES, AND NONCODING RNAS CAN CHANGE GENOME EXPRESSION UNDER THE EXOGENOUS INFLUENCE. NOTABLY, THE ROLE OF LONG NONCODING RNAS IN EPIGENETIC PROCESSES HAS NOT BEEN WELL EXPLORED IN THE CONTEXT OF EXPOSOME-INDUCED TUMORIGENESIS. IN THE PRESENT REVIEW, OUR SCOPE IS TO PROVIDE RELEVANT EVIDENCE INDICATING THAT EPIGENETIC ALTERATIONS MEDIATE THOSE DETRIMENTAL EFFECTS CAUSED BY EXPOSURE TO ENVIRONMENTAL TOXICANTS, FOCUSING MAINLY ON A MULTI-STEP REGULATION BY DIVERSE NONCODING RNAS SUBTYPES. 2022 5 738 37 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 6 1546 29 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 7 6199 34 THE IMPORTANCE OF EPIGENETICS IN THE DEVELOPMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE. IT IS GENERALLY ACCEPTED THAT GENETIC PREDISPOSITION PLAYS A ROLE IN COPD DEVELOPMENT IN SUSCEPTIBLE INDIVIDUALS. THEREFORE, MANY CANDIDATE GENES THAT COULD BE LINKED TO THE DEVELOPMENT OF DISEASE HAVE BEEN EXAMINED IN COPD. HOWEVER, INCONSISTENT RESULTS IN DIFFERENT STUDY POPULATIONS OFTEN LIMIT THIS APPROACH, SUGGESTING THAT NOT ONLY GENETICS, BUT ALSO OTHER FACTORS, MAY BE CONTRIBUTED TO THE SUSCEPTIBILITY TO COPD. EPIGENETIC MECHANISMS CAN AFFECT THE TRANSCRIPTIONAL ACTIVITY OF SPECIFIC GENES, AT DIFFERENT POINTS IN TIME, AND IN DIFFERENT ORGANS. MOREOVER, THESE MECHANISMS CAN HAVE AN EFFECT ON PEOPLE'S HEALTH. RECENTLY, THERE IS EMERGING EVIDENCE SUPPORTING A ROLE OF EPIGENETICS FOR THE REGULATION OF INFLAMMATORY GENES IN DISEASES SUCH AS ASTHMA AND COPD. MOREOVER, RECENT STUDIES SUGGEST THAT THE CURRENTLY USED TREATMENTS INCLUDING CORTICOSTEROIDS MAY WORK THROUGH EPIGENETIC MECHANISMS. EPIGENETIC REGULATION CAN BE REPROGRAMMED, POTENTIALLY AFFECTING THE RISK, AETIOLOGY AND TREATMENT OF VARIOUS DISEASE STATES. THE EPIGENETICALLY INFLUENCED PHENOTYPE COULD BE REVERSED WITH DEMETHYLATING OR DEACETYLATING AGENTS, CONSISTENT WITH EPIGENETIC PLASTICITY. THE POSTNATAL REVERSIBILITY OF THESE METHYLATION OR ACETYLATION EVENTS MAY THEREFORE PROVIDE GOOD OPPORTUNITIES FOR INTERVENTION. THE RECOGNITION OF THE ROLE OF GENETIC AND EPIGENETIC MECHANISMS IN THE DEVELOPMENT OF COPD MAY IDENTIFY NOVEL TARGETS THAT HATCH NEW THERAPIES FOR PATIENTS WITH COPD. 2011 8 5376 37 RECENT DEVELOPMENTS IN EPIGENETICS OF ACUTE AND CHRONIC KIDNEY DISEASES. THE GROWING EPIDEMIC OF OBESITY AND DIABETES, THE AGING POPULATION AS WELL AS PREVALENCE OF DRUG ABUSE HAS LED TO SIGNIFICANT INCREASES IN THE RATES OF THE CLOSELY ASSOCIATED ACUTE AND CHRONIC KIDNEY DISEASES, INCLUDING DIABETIC NEPHROPATHY. FURTHERMORE, EVIDENCE SHOWS THAT PARENTAL BEHAVIOR AND DIET CAN AFFECT THE PHENOTYPE OF SUBSEQUENT GENERATIONS VIA EPIGENETIC TRANSMISSION MECHANISMS. THESE DATA SUGGEST A STRONG INFLUENCE OF THE ENVIRONMENT ON DISEASE SUSCEPTIBILITY AND THAT, APART FROM GENETIC SUSCEPTIBILITY, EPIGENETIC MECHANISMS NEED TO BE EVALUATED TO GAIN CRITICAL NEW INFORMATION ABOUT KIDNEY DISEASES. EPIGENETICS IS THE STUDY OF PROCESSES THAT CONTROL GENE EXPRESSION AND PHENOTYPE WITHOUT ALTERATIONS IN THE UNDERLYING DNA SEQUENCE. EPIGENETIC MODIFICATIONS, INCLUDING CYTOSINE DNA METHYLATION AND COVALENT POST-TRANSLATIONAL MODIFICATIONS OF HISTONES IN CHROMATIN, ARE PART OF THE EPIGENOME, THE INTERFACE BETWEEN THE STABLE GENOME AND THE VARIABLE ENVIRONMENT. THIS DYNAMIC EPIGENETIC LAYER RESPONDS TO EXTERNAL ENVIRONMENTAL CUES TO INFLUENCE THE EXPRESSION OF GENES ASSOCIATED WITH DISEASE STATES. THE FIELD OF EPIGENETICS HAS SEEN REMARKABLE GROWTH IN THE PAST FEW YEARS WITH SIGNIFICANT ADVANCES IN BASIC BIOLOGY, CONTRIBUTIONS TO HUMAN DISEASE, AS WELL AS EPIGENOMICS TECHNOLOGIES. FURTHER UNDERSTANDING OF HOW THE RENAL CELL EPIGENOME IS ALTERED BY METABOLIC AND OTHER STIMULI CAN YIELD NOVEL NEW INSIGHTS INTO THE PATHOGENESIS OF KIDNEY DISEASES. IN THIS REVIEW, WE HAVE DISCUSSED THE CURRENT KNOWLEDGE ON THE ROLE OF EPIGENETIC MECHANISMS (PRIMARILY DNAME AND HISTONE MODIFICATIONS) IN ACUTE AND CHRONIC KIDNEY DISEASES, AND THEIR TRANSLATIONAL POTENTIAL TO IDENTIFY MUCH NEEDED NEW THERAPIES. 2015 9 2523 38 EPIGENETICS AND THE TRANSITION FROM ACUTE TO CHRONIC PAIN. OBJECTIVE: THE OBJECTIVE OF THIS STUDY WAS TO REVIEW THE EPIGENETIC MODIFICATIONS INVOLVED IN THE TRANSITION FROM ACUTE TO CHRONIC PAIN AND TO IDENTIFY POTENTIAL TARGETS FOR THE DEVELOPMENT OF NOVEL, INDIVIDUALIZED PAIN THERAPEUTICS. BACKGROUND: EPIGENETICS IS THE STUDY OF HERITABLE MODIFICATIONS IN GENE EXPRESSION AND PHENOTYPE THAT DO NOT REQUIRE A CHANGE IN GENETIC SEQUENCE TO MANIFEST THEIR EFFECTS. ENVIRONMENTAL TOXINS, MEDICATIONS, DIET, AND PSYCHOLOGICAL STRESSES CAN ALTER EPIGENETIC PROCESSES SUCH AS DNA METHYLATION, HISTONE ACETYLATION, AND RNA INTERFERENCE. AS EPIGENETIC MODIFICATIONS POTENTIALLY PLAY AN IMPORTANT ROLE IN INFLAMMATORY CYTOKINE METABOLISM, STEROID RESPONSIVENESS, AND OPIOID SENSITIVITY, THEY ARE LIKELY KEY FACTORS IN THE DEVELOPMENT OF CHRONIC PAIN. ALTHOUGH OUR KNOWLEDGE OF THE HUMAN GENETIC CODE AND DISEASE-ASSOCIATED POLYMORPHISMS HAS GROWN SIGNIFICANTLY IN THE PAST DECADE, WE HAVE NOT YET BEEN ABLE TO ELUCIDATE THE MECHANISMS THAT LEAD TO THE DEVELOPMENT OF PERSISTENT PAIN AFTER NERVE INJURY OR SURGERY. DESIGN: THIS IS A FOCUSED LITERATURE REVIEW OF EPIGENETIC SCIENCE AND ITS RELATIONSHIP TO CHRONIC PAIN. RESULTS: SIGNIFICANT LABORATORY AND CLINICAL DATA SUPPORT THE NOTION THAT EPIGENETIC MODIFICATIONS ARE AFFECTED BY THE ENVIRONMENT AND LEAD TO DIFFERENTIAL GENE EXPRESSION. SIMILAR TO MECHANISMS INVOLVED IN THE DEVELOPMENT OF CANCER, NEURODEGENERATIVE DISEASE, AND INFLAMMATORY DISORDERS, THE LITERATURE ENDORSES AN IMPORTANT POTENTIAL ROLE FOR EPIGENETICS IN CHRONIC PAIN. CONCLUSIONS: EPIGENETIC ANALYSIS MAY IDENTIFY MECHANISMS CRITICAL TO THE DEVELOPMENT OF CHRONIC PAIN AFTER INJURY, AND MAY PROVIDE NEW PATHWAYS AND TARGET MECHANISMS FOR FUTURE DRUG DEVELOPMENT AND INDIVIDUALIZED MEDICINE. 2012 10 3706 31 INFLUENCE OF GENETICS ON DISEASE SUSCEPTIBILITY AND PROGRESSION. FOR MANY CHRONIC DISEASES, THE INFLUENCE OF GENETICS IS COMPLEX AND PHENOTYPES DO NOT CONFORM TO SIMPLE MENDELIAN PATTERNS OF INHERITANCE. DISCUSSED HERE ARE TWO TYPES OF GENETIC INFLUENCES ON HEALTHY AGING. THE FIRST INVOLVES VARIATION IN THE GENE SEQUENCE ITSELF AND HOW THIS MAY INFLUENCE DISEASE SUSCEPTIBILITY, PROGRESSION, AND SEVERITY, INTERACTING WITH OTHER RECOGNIZED RISK FACTORS. THE SECOND INVOLVES EPIGENETIC REGULATORY MECHANISMS THAT MAY POTENTIALLY PROVIDE INSIGHT INTO HOW ENVIRONMENTAL INFLUENCES AFFECT THE EXPRESSED GENOME, THUS IMPROVING OUR UNDERSTANDING OF THE GENETIC MECHANISMS UNDERLYING MULTIFACTORIAL DISEASES. THE INTERLEUKIN-1 FAMILY OF CYTOKINES CAN BE USED TO ILLUSTRATE HOW GENETIC SEQUENCE VARIATION MAY AFFECT SUCH DISEASES. THIS CYTOKINE FAMILY PLAYS A KEY ROLE IN MEDIATING INFLAMMATION, WHICH IS NOW UNDERSTOOD TO BE A CENTRAL COMPONENT OF A GROWING NUMBER OF CHRONIC DISEASES. RECENT WORK HAS REVEALED MANY SEQUENCE VARIATIONS IN THE REGULATORY DNA OF GENES ENCODING IMPORTANT MEMBERS OF THE INTERLEUKIN-1 FAMILY, AND THESE VARIATIONS ARE ASSOCIATED WITH DIFFERENTIAL EFFECTS ON THE INFLAMMATORY RESPONSE. THE INTERACTIONS OF ENVIRONMENTAL FACTORS WITH BOTH DNA SEQUENCE VARIATIONS AND EPIGENETIC MODIFICATIONS ARE LIKELY TO DETERMINE THE PHENOTYPES OF MULTIFACTORIAL DISEASES OF AGING AS WELL AS THE PHENOTYPE OF HEALTHY AGING. 2007 11 6340 36 THE ROLE OF EPIGENETIC FACTORS IN PSORIASIS. PSORIASIS IS A CHRONIC, SYSTEMIC, IMMUNE-MEDIATED DISEASE WITH AN INCIDENCE OF APPROXIMATELY 2%. THE PATHOGENESIS OF THE DISEASE IS COMPLEX AND NOT YET FULLY UNDERSTOOD. GENETIC FACTORS PLAY A SIGNIFICANT ROLE IN THE PATHOGENESIS OF THE DISEASE. IN PREDISPOSED INDIVIDUALS, MULTIPLE TRIGGER FACTORS MAY CONTRIBUTE TO DISEASE ONSET AND EXACERBATIONS OF SYMPTOMS. ENVIRONMENTAL FACTORS (STRESS, INFECTIONS, CERTAIN MEDICATIONS, NICOTINISM, ALCOHOL, OBESITY) PLAY A SIGNIFICANT ROLE IN THE PATHOGENESIS OF PSORIASIS. IN ADDITION, EPIGENETIC MECHANISMS ARE CONSIDERED RESULT IN MODULATION OF INDIVIDUAL GENE EXPRESSION AND AN INCREASED LIKELIHOOD OF THE DISEASE. STUDIES HIGHLIGHT THE SIGNIFICANT ROLE OF EPIGENETIC FACTORS IN THE ETIOLOGY AND PATHOGENESIS OF PSORIASIS. EPIGENETIC MECHANISMS IN PSORIASIS INCLUDE DNA METHYLATION, HISTONE MODIFICATIONS AND NON-CODING RNAS. EPIGENETIC MECHANISMS INDUCE GENE EXPRESSION CHANGES UNDER THE INFLUENCE OF CHEMICAL MODIFICATIONS OF DNA AND HISTONES, WHICH ALTER CHROMATIN STRUCTURE AND ACTIVATE TRANSCRIPTION FACTORS OF SELECTED GENES, THUS LEADING TO TRANSLATION OF NEW MRNA WITHOUT AFFECTING THE DNA SEQUENCE. EPIGENETIC FACTORS CAN REGULATE GENE EXPRESSION AT THE TRANSCRIPTIONAL (VIA HISTONE MODIFICATION, DNA METHYLATION) AND POSTTRANSCRIPTIONAL LEVELS (VIA MICRORNAS AND LONG NON-CODING RNAS). THIS STUDY AIMS TO PRESENT AND DISCUSS THE DIFFERENT EPIGENETIC MECHANISMS IN PSORIASIS BASED ON A REVIEW OF THE AVAILABLE LITERATURE. 2021 12 6809 27 [EPIGENETICS IN INFLAMMATORY SYSTEMIC DISEASES]. IN ADDITION TO ANALYSIS OF THE GENETIC CODE, IN RECENT YEARS MORE AND MORE STUDIES HAVE CONCENTRATED ON CHANGES IN THE EPIGENETIC CODE. EPIGENETIC MECHANISMS DETERMINE WHICH GENES IN A CELL ARE TRANSCRIBED AND THUS FORM THE PHENOTYPE OF A CELL. THE EPIGENETIC CODE CAN BE CHANGED BY ENVIRONMENTAL INFLUENCES, WHICH ALLOWS CELLS TO ADAPT TO LONGSTANDING CHANGES IN THE ENVIRONMENT. THEREFORE, IT IS FEASIBLE TO ASSUME THAT EPIGENETIC CHANGES ARE THE MOLECULAR BASIS FOR LONG-TERM EFFECTS OF THE ENVIRONMENT ON DISEASE DEVELOPMENT. IN PARTICULAR IN TUMORS AND CHRONIC INFLAMMATORY DISEASES EPIGENETIC CHANGES WERE FOUND TO CORRELATE WITH DISEASE SEVERITY AND PROGRESSION. KNOWLEDGE ABOUT THESE EPIGENETIC CHANGES MIGHT HELP THAT EPIGENETIC MODIFICATIONS CAN BE USED IN THE FUTURE AS BIOMARKERS, PROGNOSTIC FACTORS AND THERAPEUTIC TARGETS. 2014 13 6288 36 THE POTENTIAL ROLE OF EPIGENETIC MODIFICATIONS ON DIFFERENT FACETS IN THE PERIODONTAL PATHOGENESIS. PERIODONTITIS IS A CHRONIC INFLAMMATORY DISEASE THAT AFFECTS THE SUPPORTING STRUCTURES OF TEETH. IN THE LITERATURE, THE ASSOCIATION BETWEEN THE PATHOGENICITY OF BACTERIA AND ENVIRONMENTAL FACTORS IN THIS REGARD HAVE BEEN EXTENSIVELY EXAMINED. IN THE PRESENT STUDY, WE WILL SHED LIGHT ON THE POTENTIAL ROLE THAT EPIGENETIC CHANGE CAN PLAY ON DIFFERENT FACETS OF ITS PROCESS, MORE PARTICULARLY THE MODIFICATIONS CONCERNING THE GENES INVOLVED IN INFLAMMATION, DEFENSE, AND IMMUNE SYSTEMS. SINCE THE 1960S, THE ROLE OF GENETIC VARIANTS IN THE ONSET AND SEVERITY OF PERIODONTAL DISEASE HAS BEEN WIDELY DEMONSTRATED. THESE MAKE SOME PEOPLE MORE SUSCEPTIBLE TO DEVELOPING IT THAN OTHERS. IT HAS BEEN DOCUMENTED THAT THE WIDE VARIATION IN ITS FREQUENCY FOR VARIOUS RACIAL AND ETHNIC POPULATIONS IS DUE PRIMARILY TO THE COMPLEX INTERPLAY AMONG GENETIC FACTORS WITH THOSE AFFECTING THE ENVIRONMENT AND THE DEMOGRAPHY. IN MOLECULAR BIOLOGY, EPIGENETIC MODIFICATIONS ARE DEFINED AS ANY CHANGE IN THE PROMOTER FOR THE CPG ISLANDS, IN THE STRUCTURE OF THE HISTONE PROTEIN, AS WELL AS POST-TRANSLATIONAL REGULATION BY MICRORNAS (MIRNAS), BEING KNOWN TO CONTRIBUTE TO THE ALTERATION IN GENE EXPRESSION FOR COMPLEX MULTIFACTORIAL DISEASES SUCH AS PERIODONTITIS. THE KEY ROLE OF EPIGENETIC MODIFICATION IS TO UNDERSTAND THE MECHANISM INVOLVED IN THE GENE-ENVIRONMENT INTERACTION, AND THE DEVELOPMENT OF PERIODONTITIS IS NOW THE SUBJECT OF MORE AND MORE STUDIES THAT ATTEMPT TO IDENTIFY WHICH FACTORS ARE STIMULATING IT, BUT ALSO AFFECT THE REDUCED RESPONSE TO THERAPY. 2023 14 6268 27 THE NEUROEPIGENOME: IMPLICATIONS OF CHEMICAL AND PHYSICAL MODIFICATIONS OF GENOMIC DNA IN SCHIZOPHRENIA. SCHIZOPHRENIA IS A CHRONIC MENTAL ILLNESS WITH A SUBSTANTIAL GENETIC COMPONENT. TO UNFOLD THE COMPLEX ETIOLOGY OF SCHIZOPHRENIA, IT IS IMPORTANT TO UNDERSTAND THE INTERPLAY BETWEEN GENETIC AND NONGENETIC FACTORS. GENETIC FACTORS INVOLVE VARIATION IN THE DNA SEQUENCES OF PROTEIN-CODING GENES, WHICH DIRECTLY CONTRIBUTE TO PHENOTYPIC TRAITS, AND VARIATION IN NONCODING SEQUENCES, WHICH COMPRISE 98% OF THE GENOME AND CONTAIN DNA ELEMENTS KNOWN TO PLAY A ROLE IN REGULATING GENE EXPRESSION. THE EPIGENOME REFERS TO THE CHEMICAL MODIFICATIONS ON BOTH DNA AND THE STRUCTURAL PROTEINS THAT PACKAGE DNA INTO THE NUCLEUS, WHICH TOGETHER REGULATE GENE EXPRESSION IN SPECIFIC CELL TYPES, CONDITIONS, AND DEVELOPMENTAL STAGES. THE DYNAMIC NATURE OF THE EPIGENOME MAKES IT AN IDEAL TOOL TO INVESTIGATE THE RELATIONSHIP BETWEEN INHERITED GENETIC MUTATIONS ASSOCIATED WITH SCHIZOPHRENIA AND ALTERED GENE REGULATION THROUGHOUT THE COURSE OF BRAIN DEVELOPMENT. IN THIS REVIEW, WE FOCUS ON THE CURRENT UNDERSTANDING OF THE ROLE OF EPIGENETIC MARKS AND THEIR THREE-DIMENSIONAL NUCLEAR ORGANIZATION IN THE DEVELOPMENTAL TRAJECTORY OF DISTINCT BRAIN CELL TYPES TO DECIPHER THE COMPLEX GENE REGULATORY MECHANISMS THAT ARE DISRUPTED IN SCHIZOPHRENIA. 2022 15 1014 31 CIGARETTE SMOKING AND DNA METHYLATION. DNA METHYLATION IS THE MOST STUDIED EPIGENETIC MODIFICATION, CAPABLE OF CONTROLLING GENE EXPRESSION IN THE CONTEXTS OF NORMAL TRAITS OR DISEASES. IT IS HIGHLY DYNAMIC DURING EARLY EMBRYOGENESIS AND REMAINS RELATIVELY STABLE THROUGHOUT LIFE, AND SUCH PATTERNS ARE INTRICATELY RELATED TO HUMAN DEVELOPMENT. DNA METHYLATION IS A QUANTITATIVE TRAIT DETERMINED BY A COMPLEX INTERPLAY OF GENETIC AND ENVIRONMENTAL FACTORS. GENETIC VARIANTS AT A SPECIFIC LOCUS CAN INFLUENCE BOTH REGIONAL AND DISTANT DNA METHYLATION. THE ENVIRONMENT CAN HAVE VARYING EFFECTS ON DNA METHYLATION DEPENDING ON WHEN THE EXPOSURE OCCURS, SUCH AS DURING PRENATAL LIFE OR DURING ADULTHOOD. IN PARTICULAR, CIGARETTE SMOKING IN THE CONTEXT OF BOTH CURRENT SMOKING AND PRENATAL EXPOSURE IS A STRONG MODIFIER OF DNA METHYLATION. EPIGENOME-WIDE ASSOCIATION STUDIES HAVE UNCOVERED CANDIDATE GENES ASSOCIATED WITH CIGARETTE SMOKING THAT HAVE BIOLOGICALLY RELEVANT FUNCTIONS IN THE ETIOLOGY OF SMOKING-RELATED DISEASES. AS SUCH, DNA METHYLATION IS A POTENTIAL MECHANISTIC LINK BETWEEN CURRENT SMOKING AND CANCER, AS WELL AS PRENATAL CIGARETTE-SMOKE EXPOSURE AND THE DEVELOPMENT OF ADULT CHRONIC DISEASES. 2013 16 5552 35 ROLE OF EPIGENETICS IN THE PATHOGENESIS OF ASTHMA. ASTHMA IS A COMPLEX, HETEROGENEOUS AND CHRONIC AIRWAY INFLAMMATORY DISEASE WITH DIFFERENT CLINICAL PHENOTYPES CAUSED BY DIVERSE TRIGGERS AND PATHOPHYSIOLOGICAL MECHANISMS. ASTHMA HERITABILITY HAS BEEN ESTABLISHED IN MANY GENETIC STUDIES BUT IT IS EVIDENT THAT ONLY GENETIC ELEMENTS ARE NOT RESPONSIBLE FOR THE DEVELOPMENT OF ASTHMA. INCREASING RATE OF ASTHMA INCIDENCE DURING PAST DECADES HAS IMPLICATED THE ROLE OF EPIGENETICS IN DEVELOPMENT OF ASTHMA. ENVIRONMENTAL FACTORS PERFORM AS INITIATOR SIGNALS THROUGH EPIGENETIC MECHANISMS. THREE EPIGENETIC MECHANISMS HAVE BEEN IDENTIFIED, INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS, AND SMALL NONCODING RNAS. THESE MECHANISMS REGULATE THE IMMUNE RESPONSES AND INFLAMMATORY GENES EXPRESSION IN ASTHMA AND ALLERGY. THIS REVIEW EXPLAINS THE ROLE OF EPIGENETIC MODIFICATIONS IN CONTROLLING TH2 RESPONSE AND IGE PRODUCTION IN ASTHMA AND ALSO BRIEFLY OVERVIEWS THE ROLE OF ENVIRONMENTAL FACTORS SUCH AS POLLUTIONS, ALLERGENS, PRENATAL EXPOSURES AND DIET IN DEVELOPING ASTHMA. RECOGNIZING ENVIRONMENTAL RISK FACTORS AND THEIR EFFECTS ON EPIGENETIC MECHANISMS WOULD BE OF GREAT INTEREST FOR PROGNOSTIC AND PREVENTIVE ASPECT IN TREATMENT OF ASTHMA. 2017 17 2648 30 EPIGENOMIC TARGETS FOR THE TREATMENT OF RESPIRATORY DISEASE. BACKGROUND: A NUMBER OF PROCESSES LEAD TO EPIGENETIC AND EPIGENOMIC MODIFICATIONS. OBJECTIVE: TO ADDRESS THE IMPORTANCE OF EPIGENOMICS IN RESPIRATORY DISEASE. METHODS: STUDIES OF EPIGENOMICS WERE ANALYSED IN RELATION TO CHRONIC RESPIRATORY DISEASES. RESULTS/CONCLUSION: IN LUNG CANCER AND MESOTHELIOMA, A NUMBER OF GENES INVOLVED IN CARCINOGENESIS HAVE BEEN DEMONSTRATED TO BE HYPERMETHYLATED, IMPLICATING EPIGENOMIC CHANGES IN THE AETIOLOGY OF THESE CANCERS. HYPERMETHYLATED GENES HAVE ALSO BEEN ASSOCIATED WITH LUNG CANCER RECURRENCE, INDICATING EPIGENOMIC REGULATION OF METASTASIS. IN AIRWAY DISEASES, MODULATION OF HISTONE FUNCTION MAY ACTIVATE INFLAMMATORY MECHANISMS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATIENTS AND LEAD TO RELATIVE STEROID RESISTANCE. THERE IS EMERGING EVIDENCE FOR THE ROLE OF EPIGENETIC CHANGES IN CHRONIC LUNG DISEASES SUCH AS ASTHMA, INCLUDING RESPONSES TO ENVIRONMENTAL EXPOSURES IN UTERO AND TO THE EFFECTS OF AIR POLLUTION. INSIGHT INTO EPIGENOMICS WILL LEAD TO THE DEVELOPMENT OF NOVEL BIOMARKERS AND TREATMENT TARGETS IN RESPIRATORY DISEASES. 2009 18 6533 34 TRANSCRIPTIONAL REGULATION OF INFLAMMATORY GENES ASSOCIATED WITH SEVERE ASTHMA. THE 10% OF PATIENTS WITH THE MOST SEVERE ASTHMA ARE RESPONSIBLE FOR A LARGE PART OF HEALTHCARE EXPENDITURE AND MORBIDITY. UNDERSTANDING THE PROCESSES INVOLVED IS KEY IF NEW THERAPEUTIC APPROACHES ARE TO BE DEVELOPED. EVIDENCE IS ACCUMULATING THAT CHRONIC DISEASES SUCH AS ASTHMA ARE ASSOCIATED WITH TEMPORAL AND SPATIAL ALTERATIONS IN THE PATTERN OF INFLAMMATORY GENE EXPRESSION WITHIN THE AIRWAYS. EXPRESSION OF THESE GENES CAN BE REGULATED BY TRANSCRIPTIONAL, POSTTRANSCRIPTIONAL, TRANSLATIONAL AND EPIGENETIC MECHANISMS. IT IS WELL ESTABLISHED THAT BINDING OF ACTIVATED TRANSCRIPTION FACTORS TO SPECIFIC INDUCIBLE GENE PROMOTER SITES IS TIGHTLY CONTROLLED BY CHROMATIN STATE AS A RESULT OF HISTONE MODIFICATIONS, PARTICULARLY THE BALANCE BETWEEN HISTONE ACETYLATION AND DEACETYLATION [1]. THE INTERACTION BETWEEN TRANSCRIPTION FACTORS AND THE PROMOTER IS KEY TO THE DIVERSIFICATION OF GENE EXPRESSION IN A TIME DEPENDENT MANNER LEADING TO ALTERED GENE EXPRESSION PROFILES. ALTERATIONS OF THE ACCESSIBILITY OF TRANSCRIPTION FACTORS TO THE DNA CAN HAVE RESIDING EFFECTS UPON GENE TRANSCRIPTION. THIS REVIEW WILL FOCUS ON THE REGULATION OF SEVERAL GROUPS OF KEY GENES WHICH ARE INVOLVED IN CHRONIC AIRWAY INFLAMMATION AND REMODELLING IN ASTHMA DRAWING MAINLY FROM OUR EXPERIENCE OF STUDYING THESE PROCESSES IN AIRWAY SMOOTH MUSCLE CELLS. AN OVERVIEW IS SHOWN IN FIGURE 1. 2011 19 3028 28 GENETICS OF COMPLEX AIRWAY DISEASE. THE PAST 3 YEARS HAVE SEEN HIGHLY SIGNIFICANT GENETIC EFFECTS IDENTIFIED FOR A WIDE VARIETY OF COMMON COMPLEX DISEASES, INCLUDING THE AIRWAY DISORDERS OF ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE. IT APPEARS THAT ONLY A PORTION OF THE GENETICALLY MEDIATED SUSCEPTIBILITY TO COMPLEX DISEASES HAS BEEN IDENTIFIED, AND THERE IS MUCH LEFT TO BE DISCOVERED. THIS REVIEW BRIEFLY DESCRIBES THE RESULTS OF THE GENOME-WIDE ASSOCIATION STUDIES OF ASTHMA AND GIVES AN OVERVIEW OF THE PARALLEL AND INCREASINGLY LARGE-SCALE STUDIES THAT ARE TAKING PLACE WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE. THE FUTURE IMPACT IS DISCUSSED OF TECHNOLOGICAL ADVANCES THAT ALLOW INCREASINGLY LARGE-SCALE GENE EXPRESSION STUDIES, NEXT-GENERATION SEQUENCING, AND GENOME-WIDE TESTING FOR EPIGENETIC EFFECTS. THE USE OF GENETIC TECHNOLOGY TO EXAMINE THE AIRWAY MICROBIOTA THAT INTERACT WITH THE MUCOSA IN HEALTH AND DISEASE IS DESCRIBED. 2011 20 2017 37 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