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

被引：31
|
作者：
Belot, Marie-Pierre [1 ,2 ]
Fradin, Delphine [1 ,2 ]
Mai, Nga [1 ,2 ]
Le Fur, Sophie [1 ,2 ]
Zelenika, Diana [3 ]
Kerr-Conte, Julie [4 ,5 ]
Pattou, Francois [4 ,5 ]
Lucas, Bruno [6 ]
Bougneres, Pierre [1 ,2 ]
机构：
[1] Univ Paris Sud, Bicetre Hosp, Pole I3E, INSERM U986, Paris, France
[2] Univ Paris Sud, Bicetre Hosp, Pole I3E, Dept Pediat Endocrinol, Paris, France
[3] Ctr Natl Genotypage, Evry, France
[4] Univ Lille Nord France, INSERM U859, Lille, France
[5] Ctr Hosp Reg Univ Lille, Lille, France
[6] Cochin Hosp, CNRS Unite Mixte Rech 8104, INSERM U1016, Paris, France
来源：
PLOS ONE | 2013年 / 8卷 / 07期
关键词：
GENOME-WIDE ASSOCIATION; TROPHOBLAST STEM-CELLS; NATURAL-KILLER-CELLS; HUMAN B-CELLS; DNA METHYLATION; GENE-EXPRESSION; T-CELLS; EPIGENETIC CONTROL; DENDRITIC CELLS; EMBRYONIC STEM;
D O I：
10.1371/journal.pone.0068093
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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 180kb 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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页数：7
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