SLC30A8 基因启动子的 DNA 甲基化增加与马来人群中的 2 型糖尿病有关。
Increased DNA methylation of the SLC30A8 gene promoter is associated with type 2 diabetes in a Malay population.
机构信息
Department of Molecular Medicine and Surgery, Rolf Luft Research Center for Diabetes and Endocrinology, M1:03 Karolinska University Hospital, Karolinska Institutet, Stockholm, Se-17176 Sweden ; Cardiovascular, Diabetes and Nutrition Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia.
Cardiovascular, Diabetes and Nutrition Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia.
出版信息
Clin Epigenetics. 2015 Mar 18;7(1):30. doi: 10.1186/s13148-015-0049-5. eCollection 2015.
BACKGROUND
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).
RESULTS
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.
CONCLUSION
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.
背景
最近的研究表明，溶质载体家族 30 成员 8（SLC30A8）基因中的 DNA 多态性赋予 2 型糖尿病（T2D）的风险易感性。本研究旨在分析该基因在 T2D 和糖尿病肾病（DN）中的 DNA 甲基化水平。
结果
我们在 992 名马来裔糖耐量正常和伴有或不伴有 DN 的 T2D 患者中证实了 SLC30A8 的遗传关联研究。采用 TaqMan 等位基因鉴别法进行基因分型。SLC30A8 基因中的 SNP rs11558471（A/G）与 T2D 强烈相关（P=0.002，OR=1.334，95%CI=1.110 至 1.602），与 DN 中度相关（P=0.041，OR=1.399，95%CI=1.013 至 1.932）。我们进一步使用亚硫酸氢盐焦磷酸测序方案对 SLC30A8 基因启动子中的六个 CpG 位点进行 DNA 甲基化分析。所有马来裔个体的 SLC30A8 基因的平均 DNA 甲基化水平约为 81.4%。与非糖尿病患者相比，T2D 患者的 SLC30A8 基因 DNA 甲基化水平更高（82.9%比 80.1%，P=0.014）。但在 T2D 患者中，伴有或不伴有 DN 的 SLC30A8 基因的 DNA 甲基化水平无显著差异。
结论
本研究首次提供证据表明，SLC30A8 基因启动子的 DNA 甲基化增加与马来人群中的 T2D 相关，但与 DN 无关。
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