AIMS Kir6.2 is found in the pancreatic B-cell, cardiac and skeletal muscle and non-vascular smooth muscle. KCNJ11, encoding Kir6.2, has been shown to be associated with both Type 2 diabetes mellitus and cardiovascular disease in several populations. In this study, we investigated whether polymorphisms in KCNJ11 are associated with Type 2 diabetes and other metabolic phenotypes in the Korean population.

METHODS We sequenced KCNJ11 to identify common polymorphisms using 24 Korean DNA samples. Of the 14 polymorphisms found in KCNJ11, six common ones [genomic sequence (g.)-1709A>T, g.-1525T>C, g.67G>A (E23K), g.570C>T (A190A), g.1009A>G (I337V), and g.1388C>T] were genotyped in 761 Type 2 diabetic patients and in 630 non-diabetic subjects.

RESULTS All the polymorphic loci in KCNJ11 are in strong linkage disequilibrium in the Korean population and act as one haplotype block. g.67G>A and g.1009A>G were associated with an increased risk of Type 2 diabetes [age, sex, and body mass index (BMI)-adjusted odds ratios (OR) = 1.376 (1.085-1.745), P = 0.008 and 1.411 (1.111-1.791), P = 0.005, respectively], as was one haplotype (A-T-A-C-G-C in the order of polymorphisms as shown above) containing g.67A and g.1009G [OR = 1.359 (1.080-1.709), P = 0.009]. The haplotype (A-T-A-C-G-C) was also strongly associated with hypertension [OR = 1.655 (1.288-2.126), P < 0.001].

CONCLUSIONS Polymorphisms in KCNJ11 are associated with Type 2 diabetes and also with hypertension in the Korean population.