Increased DNA methylation of the SLC30A8 gene promoter is associated with type 2 diabetes in a Malay population.
Increased DNA methylation of the SLC30A8 gene promoter is associated with type 2 diabetes in a Malay population.
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DOI：
10.1186/s13148-015-0049-5
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发表时间：
2015
影响因子：
5.7
通讯作者：
Gu HF
中科院分区：
文献类型：
--
作者：
Seman NA;Mohamud WN;Östenson CG;Brismar K;Gu HF
最近的研究表明，溶质载体家族30成员8(SLC30A8)基因的DNA多态性与2型糖尿病(T2D)的易感性有关。本研究旨在分析T2D和糖尿病肾病(DN)中该基因的DNA甲基化水平。我们证实了在992名糖耐量正常的马来人和患有和不患有糖尿病肾病的T2D患者中SLC30A8的基因关联研究。基因分型采用TaqMan等位基因鉴别法。SLC30A8基因SNP rs11558471(A/G)与T2D显著相关(P = 0.002，OR = 1.334，95%CI = 1.110~1.602)，与糖尿病肾病中度相关(P = 0.041，OR = 1.399，95%CI = 1.013~1.932)。我们进一步用亚硫酸氢盐焦磷酸测序法对SLC30A8基因启动子上的6个CpG位点进行了DNA甲基化分析。所有马来人SLC30A8基因的平均DNA甲基化水平约为81.4%。T2D患者SLC30A8基因甲基化水平高于非糖尿病患者(82.9%vs.80.1%，P = 0.014)。而SLC30A8基因甲基化水平在伴有和不伴有糖尿病肾病的T2D患者之间差异无统计学意义。因此，本研究提供了第一个证据，证明SLC30A8基因启动子DNA甲基化增加与T2D有关，但与糖尿病肾病无关。
Recent studies have demonstrated that DNA polymorphisms in the solute carrier family 30 member 8 (SLC30A8) gene confer the risk susceptibility to type 2 diabetes (T2D). The present study aimed to analyze DNA methylation levels of this gene in T2D and diabetic nephropathy (DN). We confirmed the genetic association study of SLC30A8 in 992 Malay subjects with normal glucose tolerance and T2D patients with and without DN. Genotyping was conducted with TaqMan allelic discrimination. SNP rs11558471(A/G) in the SLC30A8 gene was strongly associated with T2D (P = 0.002, OR = 1.334, 95% CI = 1.110 to 1.602) and moderately associated with DN (P = 0.041, OR = 1.399, 95% CI = 1.013 to 1.932). We further performed DNA methylation analysis of six CpG sites in the SLC30A8 gene promoter with bisulfite pyrosequencing protocol. The average DNA methylation levels of the SLC30A8 gene in all Malay subjects were at approximately 81.4%. DNA methylation levels of the SLC30A8 gene in T2D patients were higher compared to non-diabetic subjects (82.9% vs. 80.1%, P = 0.014). But no significant difference of DNA methylation levels of the SLC30A8 gene between T2D patients with and without DN was observed. The present study thus provides the first evidence that increased DNA methylation of the SLC30A8 gene promoter is associated with T2D but not DN in a Malay population.
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影响因子：
6.7
作者：
Drong AW;Lindgren CM;McCarthy MI
通讯作者：
McCarthy MI
影响因子：
30.8
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通讯作者：
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通讯作者：
Cohen DM
影响因子：
7.7
作者：
Chimienti, F;Devergnas, S;Seve, M
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