Background: Vitamin D and the vitamin D receptor (VDR) are associated with susceptibility to type 2 diabetes mellitus (T2DM). The purpose of the present study was to screen more single nucleotide polymorphisms (SNPs) of VDR and assess their effects on the risk of T2DM in Han Chinese.
Method: Four SNPs were genotyped in 1191 individuals (397 cases, 794 controls). Allele frequencies and genotype distributions were analyzed. Effects were investigated by evaluating genotype distribution with regard to phenotypes, insulin resistance, and β-cell function. Haplotype analysis and gene risk score (GRS) were used to evaluate the combined and additive roles of VDR SNPs on T2DM pathogenesis.
Results: There was a significant association between rs739837 and T2DM in two models and allele frequency distribution. The novel locus rs2239179 differed significantly between cases and controls, especially in males and those aged >55 years, in three models and allele frequency distribution. The TT genotype of rs739837 was associated with higher triglyceride than GG and TG genotypes, and higher total cholesterol levels than the GG genotype. Compared with the GTGA haplotype, the GCGG haplotype reduced the risk of T2DM. Trend Chi-squared tests showed that there was significant association between the weighted GRS and the risk of T2DM (Ptrend = 0.034).
Conclusion: This study provides novel evidence that rs739837 is associated with lipid metabolism in T2DM patients. The rs739837 and rs2239179 SNPs were associated with the risk of T2DM in Han Chinese. The VDR SNPs had combined and additive effects on the risk of T2DM.
Keywords: gene risk score; genetic effect evaluated; single nucleotide polymorphism; type 2 diabetes mellitus; vitamin D nuclear receptor; 遗传风险评分,遗传因素评价,单核苷酸多态性,2型糖尿病,维生素D受体基因.
© 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.