Association studies of variants in the genes involved in pancreatic beta-cell function in type 2 diabetes in Japanese subjects.
Because impaired insulin secretion is characteristic of type 2 diabetes in Asians, including Japanese, the genes involved in pancreatic beta-cell function are candidate susceptibility genes for type 2 diabetes. We examined the association of variants in genes encoding several transcription factors (TCF1, TCF2, HNF4A, ISL1, IPF1, NEUROG3, PAX6, NKX2-2, NKX6-1, and NEUROD1) and genes encoding the ATP-sensitive K(+) channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) with type 2 diabetes in a Japanese cohort of 2,834 subjects. The exon 16 -3c/t variant rs1799854 in ABCC8 showed a significant association (P = 0.0073), and variants in several genes showed nominally significant associations (P < 0.05) with type 2 diabetes. Although the E23K variant rs5219 in KCNJ11 showed no association with diabetes in Japanese (for the K allele, odds ratio [OR] 1.08 [95% CI 0.97-1.21], P = 0.15), 95% CI around the OR overlaps in meta-analysis of European populations, suggesting that our results are not inconsistent with the previous studies. This is the largest association study so far conducted on these genes in Japanese and provides valuable information for comparison with other ethnic groups.
Yokoi
Norihide
N
Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Kanamori
Masao
M
Horikawa
Yukio
Y
Takeda
Jun
J
Sanke
Tokio
T
Furuta
Hiroto
H
Nanjo
Kishio
K
Mori
Hiroyuki
H
Kasuga
Masato
M
Hara
Kazuo
K
Kadowaki
Takashi
T
Tanizawa
Yukio
Y
Oka
Yoshitomo
Y
Iwami
Yukiko
Y
Ohgawara
Hisako
H
Yamada
Yuichiro
Y
Seino
Yutaka
Y
Yano
Hideki
H
Cox
Nancy J
NJ
Seino
Susumu
S
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000483:Alleles; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology*; D005787:Gene Frequency; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D006801:Humans; D007515:Islets of Langerhans / Q000503:physiopathology*; D007564:Japan; D046228:Microarray Analysis; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D015221:Potassium Channels / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D011955:Receptors, Drug / Q000235:genetics; D017422:Sequence Analysis, DNA; D064233:Sulfonylurea Receptors; D014157:Transcription Factors / Q000235:genetics; D000099161:Kcnj11 Channel
D018528:ATP-Binding Cassette Transporters; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D014157:Transcription Factors; D000099161:Kcnj11 Channel; C577507:ABCC8 protein, human; C000715631:NKX2-2 protein, human