Common variants in KCNQ1 confer increased risk of type 2 diabetes and contribute to the diabetic epidemic in East Asians: a replication and meta-analysis.

We aimed to evaluate the effect of four common variants (rs2237892, rs2283228, rs2237895, and rs2237897) in KCNQ1 on susceptibility of type 2 diabetes (T2D) by performing a case-control study as well as a comprehensive meta-analysis. We genotyped these four variants in two sets of Chinese Han population, comprising a total of 2533 type 2 diabetic patients and 2643 nondiabetic controls. We also performed a meta-analysis of our results with published studies in East Asians, meanwhile assessing the population attributable risk (PAR) of these variants. By combining our case-control sets, a total of 45,204 T2D cases and 42,832 controls were included in the meta-analyses. The per-allele ORs ranged from 1.24 to 1.33, and the PARs ranged from 15.8% to 31.8%, with SNP rs2237892 being the most widely studied (16 articles containing a total of 38,338 cases and 35,907 controls), showing strongest association (per-allele OR: 1.33, 95% CI: 1.28-1.39) and indicating the highest PAR (31.8%). This study confirmed the strong association between common variants in KCNQ1 and risk of T2D. Variants in KCNQ1 were among the leading genetic factors contributing to the overall burden of T2D in East Asians.