Abstract: Objective The recent studies have explored several novel type 2 diabetes susceptibility variants in KCNQ1(rs2237892), AP3S1(rs3756555), MAN2A1(rs2015698) and ALDH7A1(rs2306617) genes. This study aimed to evaluate the contribution of these variants in the four genes to predisposition of type 2 diabetes in the Chinese northern Han population. Methods Four candidate single nucleotide polymorphisms, rs2237892, rs2306617, rs2015698 and rs3756555 were selected, and genotyped them in 537 unrelated individuals with type 2 diabetes and 510 normal controls. Results The C risk allele in rs2237892 and rs3756555 conferred a significantly increased susceptibility to type 2 diabetes(P=0.002, P=0.003). The significant association remains after adjusting the age, sex and BMI(OR=1.51, 95% CI: 1.17~1.95, P=0.002; OR=1.48, 95%CI: 1.14~1.92, P=0.003). No association was observed in recessive genetic models for rs2015698 and rs2306617. Further investigation in the control subjects showed that fasting plasma glucose was significantly higher for the individuals with CC genotype of rs2237892 than for those with the other two genotypes after adjusting for age, sex and BMI(P=0.020). The SNP of rs3756555 was marginally associated with BMI in recessive model(P=0.050). Conclusion In this study the effects of KCNQ1 and AP3S1 variants on the susceptibility to type 2 diabetes in the Chinese northern Han population were confirmed.

Key words: type 2 diabetes mellitus, KCNQ1, AP3S1, fasting plasma glucose