Journal Article

Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus

Park, Kyong Soo, Tanahashi, Toshihito, Maeda, Eiichi, Makino, Hideichi, Miyake, Kazuaki, Chan, Juliana C N, Yamamoto, Ken, Iwamoto, Yasuhiko, Takeda, Jun, Ma, Ronald C W, Horikawa, Yukio, Hara, Kazuo, Maegawa, Hiroshi, Nakamura, Yusuke, Kadowaki, Takashi, Lyssenko, Valeriya, Nakamura, Naoto, Hirota, Yushi, So, Wing-Yee, Furuta, Hiroto, Kashiwagi, Atsunori, Itakura, Mitsuo, Nanjo, Kishio, Nilsson, Peter, Groop, Leif, Kamatani, Naoyuki, Cho, Young Min, Ng, Maggie C Y, Sekine, Akihiro, Tokunaga, Katsushi, Iwasaki, Naoko, Seino, Yutaka, Yasuda, Kazuki, Jonsson, Anna, Oka, Yoshitomo, Sato, Yoshifumi, Wang, He-Yao, Hinokio, Yoshinori, Yamada, Yuichiro, Mori, Hiroyuki, Yoshida, Teruhiko, Kasuga, Masato, Yamagata, Kazuya, Lee, Hong Kyu, Osawa, Haruhiko, Shin, Hyoung Doo, Tuomi, Tiinamaija

2008

Overview

Masato Kasuga and colleagues and Shiro Maeda and colleagues each report the independent identification of SNPs in KCNQ1 associated with type 2 diabetes in the Japanese population. Each group replicated the associations in other populations of East Asian and European descent. 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 P value (6.7 × 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 × 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 β-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Agriculture / Alzheimer's disease / Animal Genetics and Genomics / Annan klinisk medicin / Asian Continental Ancestry Group - genetics / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Cancer Research / Chromosome Mapping / Clinical Medicine / Diabetes / Diabetes Mellitus, Type 2 - genetics / Diabetes. Impaired glucose tolerance / Disease susceptibility / Endocrine pancreas. Apud cells (diseases) / Endocrinology and Diabetes / Endocrinopathies / Endokrinologi och diabetes / Etiopathogenesis. Screening. Investigations. Target tissue resistance / European Continental Ancestry Group / Fundamental and applied biological sciences. Psychology / Gene Function / Genetic aspects / Genetic Predisposition to Disease / Genetic variation / Genetics of eukaryotes. Biological and molecular evolution / Genome-Wide Association Study / Genomics / Human Genetics / Humans / Insulin-Secreting Cells - physiology / KCNQ1 Potassium Channel - genetics / Klinisk medicin / letter / Medical and Health Sciences / Medical sciences / Medicin och hälsovetenskap / Other Clinical Medicine / Polymorphism, Single Nucleotide / Risk factors / Science / Type 2 diabetes