CpG Methylation Changes within the IL2RA Promoter in Type 1 Diabetes of Childhood Onset

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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.

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Belot, M. P., Fradin, D., Mai, N., Le Fur, S., Zélénika, D., Kerr-Conte, J., … Bougnères, P. (2013). CpG Methylation Changes within the IL2RA Promoter in Type 1 Diabetes of Childhood Onset. PLoS ONE, 8(7). https://doi.org/10.1371/journal.pone.0068093

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