CpG methylation changes within the IL2RA promoter in type 1 diabetes of childhood onset.
case_control · Level III
Where this comes from
- Record sourced from PubMed, PMID 23874506.
- Also identified by DOI 10.1371/journal.pone.0068093 and PMC identifier 3709990.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- CpG Islands
- DNA Methylation
- Diabetes Mellitus, Type 1
- Genetic Predisposition to Disease
- Interleukin-2 Receptor alpha Subunit
- Promoter Regions, Genetic