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.

引用

页数：7

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