Increased dna methylation of the slc30a8 gene promoter is associated with type 2 diabetes in a malay population

Abstract

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.