S-Space College of Medicine/School of Medicine (의과대학/대학원) Internal Medicine (내과학전공) Journal Papers (저널논문_내과학전공)
Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus
- Yasuda, Kazuki ; Miyake, Kazuaki ; Horikawa, Yukio ; Hara, Kazuo ; Osawa, Haruhiko ; Furuta, Hiroto ; Hirota, Yushi ; Mori, Hiroyuki ; Jonsson, Anna ; Sato, Yoshifumi ; Yamagata, Kazuya ; Hinokio, Yoshinori ; Wang, He-Yao ; Tanahashi, Toshihito ; Nakamura, Naoto ; Oka, Yoshitomo ; Iwasaki, Naoko ; Iwamoto, Yasuhiko ; Yamada, Yuichiro ; Seino, Yutaka ; Maegawa, Hiroshi ; Kashiwagi, Atsunori ; Takeda, Jun ; Maeda, Eiichi ; Shin, Hyoung Doo ; Cho, Young Min ; Park, Kyong Soo ; Lee, Hong Kyu ; Ng, Maggie C Y ; Ma, Ronald C W ; So, Wing-Yee ; Chan, Juliana C N ; Lyssenko, Valeriya ; Tuomi, Tiinamaija ; Nilsson, Peter ; Groop, Leif ; Kamatani, Naoyuki ; Sekine, Akihiro ; Nakamura, Yusuke ; Yamamoto, Ken ; Yoshida, Teruhiko ; Tokunaga, Katsushi ; Itakura, Mitsuo ; Makino, Hideichi ; Nanjo, Kishio ; Kadowaki, Takashi ; Kasuga, Masato
- Issue Date
- Nature Publishing Group
- Nat Genet. 2008 ;40(9):1092-7.
- Asian Continental Ancestry Group/genetics ; Chromosome Mapping ; Diabetes Mellitus, Type 2/*genetics ; European Continental Ancestry Group ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Insulin-Secreting Cells/physiology ; KCNQ1 Potassium Channel/*genetics ; Polymorphism, Single Nucleotide
- We carried out a multistage genome-wide association study of type 2 diabetes mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls and 100,000 SNPs. The most significant association was obtained with SNPs in KCNQ1, and dense mapping within the gene revealed that rs2237892 in intron 15 showed the lowest Pvalue (6.7 x 10(-13), odds ratio (OR) = 1.49). The association of KCNQ1 with type 2 diabetes was replicated in populations of Korean, Chinese and European ancestry as well as in two independent Japanese populations, and meta-analysis with a total of 19,930 individuals (9,569 cases and 10,361 controls) yielded a P value of 1.7 x 10(-42) (OR = 1.40; 95% CI = 1.34-1.47) for rs2237892. Among control subjects, the risk allele of this polymorphism was associated with impairment of insulin secretion according to the homeostasis model assessment of beta-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries.
- 1061-4036 (Print)
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