The E23K Variation in the KCNJ11 Gene is Associated with Type 2 Diabetes in Chinese and East Asian Population

The genes (ABCC8 and KCNJ11) have a key role in glucose-stimulated insulin secretion and thus have always been considered as excellent susceptibility candidates for involvement in type 2 diabetes. Common polymorphisms (KCNJ11 E23K and ABCC8 exon16-3t/c) in these genes have been reported to be associated with type 2 diabetes in various European-descent populations. However, there were inconsistent results in previous studies in East Asian populations and no large case-control studies have been carried out in the Chinese Han population. In this study, these two variants were genotyped in about 4000 Chinese by using TaqMan technology on an ABI7900 system. A meta-analysis was also used to assess the results of association between the two variants and type 2 diabetes in East Asian populations. Our investigation confirmed the association between the KCNJ11 E23K variant and type 2 diabetes under a recessive model (KK vs EK+EE) in the Chinese Han population (odds ratio (OR)=1.25, 95% confidence interval (95% CI) 1.04-1.50, P=0.017). The meta-analysis of East Asian populations also showed a strong significant association of the K allele with diabetes (OR=1.15, P=3 x 10(-9)), whereas the exon16-3t/c variant (rs1799854) in ABCC8 showed no significant association. Thus, the common E23K variant is considered as a strong candidate for type 2 diabetes susceptibility across different ethnicities.