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

Authors :
Yasuda, Kazuki
Miyake, Kazuaki
Horikawa, Yukio
Hara, Kazuo
Osawa, Haruhiko
Furuta, Hiroto
Hirota, Yushi
Mori, Hiroyuki
Jonsson, Anna Elisabet
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
Yasuda, Kazuki
Miyake, Kazuaki
Horikawa, Yukio
Hara, Kazuo
Osawa, Haruhiko
Furuta, Hiroto
Hirota, Yushi
Mori, Hiroyuki
Jonsson, Anna Elisabet
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
Source :
Yasuda , K , Miyake , K , Horikawa , Y , Hara , K , Osawa , H , Furuta , H , Hirota , Y , Mori , H , Jonsson , A E , Sato , Y , Yamagata , K , Hinokio , Y , Wang , H-Y , Tanahashi , T , Nakamura , N , Oka , Y , Iwasaki , N , Iwamoto , Y , Yamada , Y , Seino , Y , Maegawa , H , Kashiwagi , A , Takeda , J , Maeda , E , Shin , H D , Cho , Y M , Park , K S , Lee , H K , Ng , M C Y , Ma , R C W , So , W-Y , Chan , J C N , Lyssenko , V , Tuomi , T , Nilsson , P , Groop , L , Kamatani , N , Sekine , A , Nakamura , Y , Yamamoto , K , Yoshida , T , Tokunaga , K , Itakura , M , Makino , H , Nanjo , K , Kadowaki , T & Kasuga , M 2008 , ' Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus ' , Nature Genetics , vol. 40 , no. 9 , pp. 1092-7 .
Publication Year :
2008

Abstract

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.

Details

Database :
OAIster
Journal :
Yasuda , K , Miyake , K , Horikawa , Y , Hara , K , Osawa , H , Furuta , H , Hirota , Y , Mori , H , Jonsson , A E , Sato , Y , Yamagata , K , Hinokio , Y , Wang , H-Y , Tanahashi , T , Nakamura , N , Oka , Y , Iwasaki , N , Iwamoto , Y , Yamada , Y , Seino , Y , Maegawa , H , Kashiwagi , A , Takeda , J , Maeda , E , Shin , H D , Cho , Y M , Park , K S , Lee , H K , Ng , M C Y , Ma , R C W , So , W-Y , Chan , J C N , Lyssenko , V , Tuomi , T , Nilsson , P , Groop , L , Kamatani , N , Sekine , A , Nakamura , Y , Yamamoto , K , Yoshida , T , Tokunaga , K , Itakura , M , Makino , H , Nanjo , K , Kadowaki , T & Kasuga , M 2008 , ' Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus ' , Nature Genetics , vol. 40 , no. 9 , pp. 1092-7 .
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1322631441
Document Type :
Electronic Resource