SNPs in the KCNJ11-ABCC8 gene locus are associated with type 2 diabetes and blood pressure levels in the Japanese population.
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.
Sakamoto
Yukiko
Y
Division of Genetic Information, Institute for Genome Research, The University of Tokushima, #3-18-15, Kuramoto-cho, Tokushima-city, Tokushima, 770-8503, Japan.
Inoue
Hiroshi
H
Division of Genetic Information, Institute for Genome Research, The University of Tokushima, #3-18-15, Kuramoto-cho, Tokushima-city, Tokushima, 770-8503, Japan. hinoue@genome.tokushima-u.ac.jp.
Keshavarz
Parvaneh
P
Division of Genetic Information, Institute for Genome Research, The University of Tokushima, #3-18-15, Kuramoto-cho, Tokushima-city, Tokushima, 770-8503, Japan.
Miyawaki
Katsuyuki
K
Division of Genetic Information, Institute for Genome Research, The University of Tokushima, #3-18-15, Kuramoto-cho, Tokushima-city, Tokushima, 770-8503, Japan.
Yamaguchi
Yuka
Y
Division of Genetic Information, Institute for Genome Research, The University of Tokushima, #3-18-15, Kuramoto-cho, Tokushima-city, Tokushima, 770-8503, Japan.
Moritani
Maki
M
Division of Genetic Information, Institute for Genome Research, The University of Tokushima, #3-18-15, Kuramoto-cho, Tokushima-city, Tokushima, 770-8503, Japan.
Kunika
Kiyoshi
K
Division of Genetic Information, Institute for Genome Research, The University of Tokushima, #3-18-15, Kuramoto-cho, Tokushima-city, Tokushima, 770-8503, Japan.
Nakamura
Naoto
N
Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Yoshikawa
Toshikazu
T
Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Yasui
Natsuo
N
Department of Orthopedics, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan.
Shiota
Hiroshi
H
Department of Ophthalmology and Visual Neuroscience, Institute for Health Biosciences, The University of Tokushima, Tokushima, Japan.
Tanahashi
Toshihito
T
Division of Genetic Information, Institute for Genome Research, The University of Tokushima, #3-18-15, Kuramoto-cho, Tokushima-city, Tokushima, 770-8503, Japan.
Itakura
Mitsuo
M
Division of Genetic Information, Institute for Genome Research, The University of Tokushima, #3-18-15, Kuramoto-cho, Tokushima-city, Tokushima, 770-8503, Japan.
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000368:Aged; D044466:Asian People / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015221:Potassium Channels / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011955:Receptors, Drug / Q000235:genetics*; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel