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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Age of Onset
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Case-Control Studies
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Child
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CpG Islands / genetics*
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DNA Methylation / genetics*
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Diabetes Mellitus, Type 1 / epidemiology*
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Diabetes Mellitus, Type 1 / genetics*
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Female
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France / epidemiology
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Genetic Association Studies
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Genetic Loci / genetics
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Genetic Predisposition to Disease*
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Humans
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Interleukin-2 Receptor alpha Subunit / genetics*
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Male
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Polymorphism, Single Nucleotide / genetics
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Promoter Regions, Genetic*
Substances
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IL2RA protein, human
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Interleukin-2 Receptor alpha Subunit
Grants and funding
This study was supported by “Alliance Diabète de Type 1 NovoNordisk-INSERM” program, Centre National de Génotypage (Evry), Association pour la Recherche sur le Diabète, Programme Hospitalier de Recherche Clinique; by a grant from Association pour la Recherche sur le Diabète (ARD grant 2012 to DF), and NovoNordisk France (“Alliance” 2010–2013 to PB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.