title: CpG methylation changes within the IL2RA promoter in type 1 diabetes of childhood onset.
abstract: None of the polymorphic variants of the IL2RA gene found associated with Type 1 Diabetes (T1D) was shown to have a functional effect. To test if the epigenetic variation could play a role at this locus, we studied the methylation of 6 CpGs located within the proximal promoter of IL2RA gene in 252 T1D patients compared with 286 age-matched controls. We found that DNA methylation at CpGs -373 and -456 was slightly but significantly higher in patients than in controls (40.4 ± 4.6 vs 38.3 ± 5.4, p=1.4E4; 91.4 ± 2.8 vs 89.5 ± 5.3, p=1.8E-6), while other CpG showed a strictly comparable methylation. Among 106 single nucleotide polymorphisms (SNPs) located in the neighboring 180 kb region, we found that 28 SNPs were associated with DNA methylation at CpG -373. Sixteen of these SNPs were known to be associated with T1D. Our findings suggest that the effect of IL2RA risk alleles on T1D may be partially mediated through epigenetic changes.
authors.affiliation: INSERM U986 and Department of Pediatric Endocrinology, Bicêtre Hospital, Pôle I3E, Paris Sud University, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Belot
authors.forename: Delphine
authors.initials: D
authors.lastname: Fradin
authors.forename: Nga
authors.initials: N
authors.lastname: Mai
authors.forename: Sophie
authors.initials: S
authors.lastname: Le Fur
authors.forename: Diana
authors.initials: D
authors.lastname: Zélénika
authors.forename: Julie
authors.initials: J
authors.lastname: Kerr-Conte
authors.forename: François
authors.initials: F
authors.lastname: Pattou
authors.forename: Bruno
authors.initials: B
authors.lastname: Lucas
authors.forename: Pierre
authors.initials: P
authors.lastname: Bougnères
mesh_terms: D017668:Age of Onset; D016022:Case-Control Studies; D002648:Child; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005602:France / Q000453:epidemiology; D056726:Genetic Association Studies; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic
chemical_list: C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit