title: Epigenetics in type 1 diabetes: TNFa gene promoter methylation status in Chilean patients with type 1 diabetes mellitus.
abstract: TNF-α is a pro-inflammatory cytokine that is involved in type 1 diabetes (T1D) pathogenesis. The TNFa gene is subject of epigenetic regulation in which folate and homocysteine are important molecules because they participate in the methionine cycle where the most important methyl group donor (S-adenosylmethionine) is formed. We investigated whether TNFa gene promoter methylation status in T1D patients was related to blood folate, homocysteine and TNF-α in a transversal case-control study. We studied T1D patients (n 25, mean=13·7 years) and healthy control subjects (n 25, mean=31·1 years), without T1D and/or other autoimmune diseases or direct family history of these diseases. A blood sample was obtained for determination of serum folate, plasma homocysteine and TNF-α concentrations. Whole blood was used for the extraction of DNA to determine the percentage of methylation by real-time PCR and melting-curve analysis. Results are expressed as means and standard deviations for parametric variables and as median (interquartile range) for non-parametric variables. T1D patients showed a higher TNFa gene promoter methylation (39·2 (sd 19·5) %) when compared with control subjects (25·4 (sd 13·7) %) (P=0·008). TNFa gene promoter methylation was positively associated only with homocysteine levels in T1D patients (r 0·55, P=0·007), but not in control subjects (r -0·122, P=0·872). To our knowledge, this is the first work that reports the methylation status of the TNFa gene promoter and its relationship with homocysteine metabolism in Chilean T1D patients without disease complications.
authors.affiliation: 1Nutrigenomics Laboratory,Department of Nutrition,School of Medicine,University of Chile,Av. Independencia 1027,Santiago 8380453,Chile.
authors.forename: Viviana
authors.initials: V
authors.lastname: Arroyo-Jousse
authors.affiliation: 1Nutrigenomics Laboratory,Department of Nutrition,School of Medicine,University of Chile,Av. Independencia 1027,Santiago 8380453,Chile.
authors.forename: Diego F
authors.initials: DF
authors.lastname: Garcia-Diaz
authors.affiliation: 2Institute of Maternal and Child Research,School of Medicine,University of Chile,Av. Santa Rosa 1234,Santiago 8360160,Chile.
authors.forename: Ethel
authors.initials: E
authors.lastname: Codner
authors.affiliation: 1Nutrigenomics Laboratory,Department of Nutrition,School of Medicine,University of Chile,Av. Independencia 1027,Santiago 8380453,Chile.
authors.forename: Francisco
authors.initials: F
authors.lastname: Pérez-Bravo
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D002677:Chile; D019175:DNA Methylation; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005260:Female; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D009691:Nucleic Acid Denaturation; D063766:Pediatric Obesity / Q000150:complications; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D006710:Homocysteine; D005492:Folic Acid
keywords:  Hcy homocysteine;  T1D type 1 diabetes; Epigenetics; Homocysteine; Methylation; TNF-α
              ; Type 1 diabetes