Many genetic association studies support a contribution of genetic variants in the
KCNJ11-
ABCC8 gene locus to type 2 diabetes (T2D) susceptibility in Caucasians. In non-Caucasian populations, however, there have been
only a few association studies, and discordant results were obtained. Herein, we selected a total of 31 SNPs covering a 211.3-kb
region of the
KCNJ11-
ABCC8 locus, characterized the patterns of linkage disequilibrium (LD) and haplotype structure, and performed a case-control association
study in a Japanese population consisting of 909 T2D patients and 893 control subjects. We found significant associations
between eight SNPs, including the
KCNJ11 E23K and
ABCC8 S1369A variants, and T2D. These disease-associated SNPs were genetically indistinguishable because of the presence of strong
LD, as found previously in Caucasians. For the
KCNJ11 E23K variant, the most significant association was obtained under a dominant genetic model (OR 1.32, 95% CI 1.09–1.60,
P = 0.004). A meta-analysis of East Asian studies, comprising a total of 3,357 T2D patients (77.4% Japanese) and 2,836 control
subjects (77.8% Japanese), confirmed the significant role of the
KCNJ11 E23K variant in T2D susceptibility. Furthermore, we found evidence suggesting that the
KCNJ11 E23K genotype is independently associated with higher blood-pressure levels.
Keywords Type 2 diabetes -
KCNJ11
-
ABCC8
- Genetic association study - Japanese population - Blood pressure