title: Association studies of variants in the genes involved in pancreatic beta-cell function in type 2 diabetes in Japanese subjects.
abstract: 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.
authors.affiliation: Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Norihide
authors.initials: N
authors.lastname: Yokoi
authors.forename: Masao
authors.initials: M
authors.lastname: Kanamori
authors.forename: Yukio
authors.initials: Y
authors.lastname: Horikawa
authors.forename: Jun
authors.initials: J
authors.lastname: Takeda
authors.forename: Tokio
authors.initials: T
authors.lastname: Sanke
authors.forename: Hiroto
authors.initials: H
authors.lastname: Furuta
authors.forename: Kishio
authors.initials: K
authors.lastname: Nanjo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mori
authors.forename: Masato
authors.initials: M
authors.lastname: Kasuga
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hara
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Yukio
authors.initials: Y
authors.lastname: Tanizawa
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Oka
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Iwami
authors.forename: Hisako
authors.initials: H
authors.lastname: Ohgawara
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Seino
authors.forename: Hideki
authors.initials: H
authors.lastname: Yano
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.forename: Susumu
authors.initials: S
authors.lastname: Seino
mesh_terms: 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
chemical_list: 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