PLoS ONE (Jan 2013)

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

  • Marie-Pierre Belot,
  • Delphine Fradin,
  • Nga Mai,
  • Sophie Le Fur,
  • Diana Zélénika,
  • Julie Kerr-Conte,
  • François Pattou,
  • Bruno Lucas,
  • Pierre Bougnères

DOI
https://doi.org/10.1371/journal.pone.0068093
Journal volume & issue
Vol. 8, no. 7
p. e68093

Abstract

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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.