Meta-analysis of GWAS in East Asian populations had established 10 loci that were associated with type 2 diabetes. Eight of them were with genome-wide significance and two with a border line association. Since these data have not been studied in an independent Han Chinese population, we aimed to investigate the association of these susceptibility loci with type 2 diabetes in an independent Han Chinese population. We executed a case-control study in 2 000 Chinese by the SNPscan method. Firstly, the repetitive sequences of 10 loci were assessed. Next, we investigated the association of 8 SNPs out of 10 with type 2 diabetes and constructed the GRS of those 8 SNPs. Finally, the relationship of the 8 loci and diabetes-related traits was analyzed. Based on the fact, that highly repetitive sequences were detected in 2 SNPs, we investigated the remaining 8 SNPs. With the exception of four SNPs (CMIP rs16955379, PEPD rs3786897, PSMD6 rs831571, ZFAND3 rs9470794), the other SNPs had the same direction of effect (odds ratio [OR]>1.0) as in the original reports, especially GLIS3 rs7041847 and KCNK16 rs1535500 were significantly associated with type 2 diabetes (rs1535500: p=0.005, OR=1.224, 95% CI 1.062–1.409; rs7041847: p=0.035, OR=1.118, 95% CI 1.070–1.388). The GRS constructed from the 8 SNPs was significantly associated with type 2 diabetes in the Chinese population (p=0.004, OR=1.065, 95% CI: 1.021–1.111). Among the participants with 24≤BMI<28 kg/m2 the 8 SNPs were significantly associated with type 2 diabetes (p=0.040, OR=1.079, 95% CI: 1.003–1.160). In quantitative trait analyses, WWOX rs17797882 was associated with decreased HOMA-β and increased level of TG and HDL-Ch, while PEPD rs3786897 and MAEA rs6815464 were associated with decreased fasting plasma glucose, and KCNK16 rs1535500 has shown a significant association with increased T-Ch and PSMD6 rs831571 had a significant association with decreased HDL-Ch. In Conclusion, with high probability the 8 loci identified in the East Asian GWAS meta-analysis are associated with type 2 diabetes in the Han Chinese population.

UBE2E2 encodes ubiquitin-conjugating enzyme E2E2, which plays an important role in the synthesis and secretion of insulin. Two previous studies indicated that SNPs in UBE2E2 were associated with risk for type 2 diabetes mellitus (T2DM) in the Japanese and Korean populations, respectively. We examined the association of one SNP in this gene, rs7612463, with the risk of T2DM in 1957 Han participants in northeastern China, using an SNPscan(TM) Kit. rs7612463 genotype was significantly associated with risk for T2DM under various genetic models, including an additive model (P = 0.004), a dominant model (P = 0.024), and a recessive model (P = 0.008). The AA genotype was associated with a significantly decreased risk for T2DM (P = 0.004, OR = 0.513, 95% CI = 0.325-0.810) after adjustment for age, gender, and BMI. The heterozygous genotype, AC, was associated with increased risk for total cholesterol (mmol l-1; P = 0.031) and triglycerides (mmol l-1; P = 0.039) in control individuals. Our results show that rs7612463 is associated with T2DM, with homozygotes of the AA genotype at decreased risk for T2DM in the Chinese population. Additionally, heterozygotes may have decreased risk of T2DM due to insulin resistance.

Background:A study has identified several novel susceptibility variants of the mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) gene for type 2 diabetes mellitus (T2DM) within the German population. Among the variants, five single nucleotide polymorphisms (SNPs) of MAP4K4 (rs1003376, rs11674694, rs2236935, rs2236936, and rs6543087) showed significant association with T2DM or diabetes-related quantitative traits. We aimed to evaluate whether common SNPs in the MAP4K4 gene were associated with T2DM in the Chinese population.Methods:Five candidate SNPs were genotyped in 996 patients newly diagnosed with T2DM and in 976 control subjects, using the SNPscan™ method. All subjects were recruited from the Second Affiliated Hospital, Harbin Medical University from October 2010 to September 2013. We evaluated the T2DM risk conferred by individual SNPs and haplotypes using logistic analysis, and the association between the five SNPs and metabolic traits in the subgroups.Results:Of the five variants, SNP rs2236935T/C was significantly associated with T2DM in this study population (odds ratio = 1.293; 95% confidence interval: 1.034–1.619, P = 0.025). In addition, among the controls, rs1003376 was significantly associated with an increased body mass index (P = 0.045) and homeostatic model assessment-insulin resistance (P = 0.037).Conclusions:MAP4K4 gene is associated with T2DM in a Chinese Han population, and MAP4K4 gene variants may contribute to the risk toward the development of T2DM.