CpG methylation changes within the IL2RA promoter in type 1 diabetes of childhood onset

• Published in: PloS one 2013-07, Vol.8 (7), p.e68093
• Main Authors: Belot, Marie-Pierre, Fradin, Delphine, Mai, Nga, Le Fur, Sophie, Zélénika, Diana, Kerr-Conte, Julie, Pattou, François, Lucas, Bruno, Bougnères, Pierre
• Format: Article
• Language: English
• Subjects: Age of Onset; Antigens; Autoimmune diseases; Biochemistry, Molecular Biology; Biology; Case-Control Studies; Child; Childhood; Children; Comparative analysis; CpG islands; CpG Islands - genetics; Cytokines; Dendritic cells; Deoxyribonucleic acid; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 1 - epidemiology; Diabetes Mellitus, Type 1 - genetics; DNA; DNA methylation; DNA Methylation - genetics; Endocrinology; Endocrinology and metabolism; Epigenetic inheritance; Epigenetics; Female; France - epidemiology; Gene expression; Genes; Genetic aspects; Genetic Association Studies; Genetic Loci - genetics; Genetic Predisposition to Disease; Human health and pathology; Humans; Interleukin 2 receptors; Interleukin-2 Receptor alpha Subunit - genetics; Life Sciences; Lymphocytes; Male; Medicine; Methylation; Molecular biology; Patients; Pediatrics; Polymorphism, Single Nucleotide - genetics; Promoter Regions, Genetic; Promoters (Genetics); Single nucleotide polymorphisms; Single-nucleotide polymorphism; Type 1 diabetes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0068093

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.