Identification of KCNJ15 as a susceptibility gene in Asian patients with type 2 diabetes mellitus

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Identification of KCNJ15 as a susceptibility gene in Asian patients with type 2 diabetes mellitus. / Okamoto, Koji; Iwasaki, Naoko; Nishimura, Chisa; Doi, Kent; Noiri, Eisei; Nakamura, Shinko; Takizawa, Miho; Ogata, Makiko; Fujimaki, Risa; Grarup, Niels; Pisinger, Charlotta; Borch-Johnsen, Knut; Lauritzen, Torsten; Sandbaek, Annelli; Hansen, Torben; Yasuda, Kazuki; Osawa, Haruhiko; Nanjo, Kishio; Kadowaki, Takashi; Kasuga, Masato; Pedersen, Oluf; Fujita, Toshiro; Kamatani, Naoyuki; Iwamoto, Yasuhiko; Tokunaga, Katsushi.

In: American Journal of Human Genetics, Vol. 86, No. 1, 2010, p. 54-64.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Okamoto, K, Iwasaki, N, Nishimura, C, Doi, K, Noiri, E, Nakamura, S, Takizawa, M, Ogata, M, Fujimaki, R, Grarup, N, Pisinger, C, Borch-Johnsen, K, Lauritzen, T, Sandbaek, A, Hansen, T, Yasuda, K, Osawa, H, Nanjo, K, Kadowaki, T, Kasuga, M, Pedersen, O, Fujita, T, Kamatani, N, Iwamoto, Y & Tokunaga, K 2010, 'Identification of KCNJ15 as a susceptibility gene in Asian patients with type 2 diabetes mellitus', American Journal of Human Genetics, vol. 86, no. 1, pp. 54-64. https://doi.org/10.1016/j.ajhg.2009.12.009

APA

Okamoto, K., Iwasaki, N., Nishimura, C., Doi, K., Noiri, E., Nakamura, S., Takizawa, M., Ogata, M., Fujimaki, R., Grarup, N., Pisinger, C., Borch-Johnsen, K., Lauritzen, T., Sandbaek, A., Hansen, T., Yasuda, K., Osawa, H., Nanjo, K., Kadowaki, T., ... Tokunaga, K. (2010). Identification of KCNJ15 as a susceptibility gene in Asian patients with type 2 diabetes mellitus. American Journal of Human Genetics, 86(1), 54-64. https://doi.org/10.1016/j.ajhg.2009.12.009

Vancouver

Okamoto K, Iwasaki N, Nishimura C, Doi K, Noiri E, Nakamura S et al. Identification of KCNJ15 as a susceptibility gene in Asian patients with type 2 diabetes mellitus. American Journal of Human Genetics. 2010;86(1):54-64. https://doi.org/10.1016/j.ajhg.2009.12.009

Author

Okamoto, Koji ; Iwasaki, Naoko ; Nishimura, Chisa ; Doi, Kent ; Noiri, Eisei ; Nakamura, Shinko ; Takizawa, Miho ; Ogata, Makiko ; Fujimaki, Risa ; Grarup, Niels ; Pisinger, Charlotta ; Borch-Johnsen, Knut ; Lauritzen, Torsten ; Sandbaek, Annelli ; Hansen, Torben ; Yasuda, Kazuki ; Osawa, Haruhiko ; Nanjo, Kishio ; Kadowaki, Takashi ; Kasuga, Masato ; Pedersen, Oluf ; Fujita, Toshiro ; Kamatani, Naoyuki ; Iwamoto, Yasuhiko ; Tokunaga, Katsushi. / Identification of KCNJ15 as a susceptibility gene in Asian patients with type 2 diabetes mellitus. In: American Journal of Human Genetics. 2010 ; Vol. 86, No. 1. pp. 54-64.

Bibtex

@article{0c8b83fae8524496b3e41d3ab1e9b702,
title = "Identification of KCNJ15 as a susceptibility gene in Asian patients with type 2 diabetes mellitus",
abstract = "Recent advances in genome research have enabled the identification of new genomic variations that are associated with type 2 diabetes mellitus (T2DM). Via fine mapping of SNPs in a candidate region of chromosome 21q, the current study identifies potassium inwardly-rectifying channel, subfamily J, member 15 (KCNJ15) as a new T2DM susceptibility gene. KCNJ15 is expressed in the beta cell of the pancreas, and a synonymous SNP, rs3746876, in exon 4 (C566T) of this gene, with T allele frequency among control subjects of 3.1%, showed a significant association with T2DM affecting lean individuals in three independent Japanese sample sets (p = 2.5 x 10(-7), odds ratio [OR] = 2.54, 95% confidence interval [CI] = 1.76-3.67) and with unstratified T2DM (p = 6.7 x 10(-6), OR = 1.76, 95% CI = 1.37-2.25). The diabetes risk allele frequency was, however, very low among Europeans in whom no association between this variant and T2DM could be shown. Functional analysis in human embryonic kidney 293 cells demonstrated that the risk allele of the synonymous SNP in exon 4 increased KCNJ15 expression via increased mRNA stability, which resulted in the higher expression of protein as compared to that of the nonrisk allele. We also showed that KCNJ15 is expressed in human pancreatic beta cells. In conclusion, we demonstrated a significant association between a synonymous variant in KCNJ15 and T2DM in lean Japanese patients with T2DM, suggesting that KCNJ15 is a previously unreported susceptibility gene for T2DM among Asians.",
keywords = "Adult, Aged, Asian Continental Ancestry Group, Case-Control Studies, Chromosomes, Human, Pair 21, Diabetes Mellitus, Type 2, Female, Genetic Predisposition to Disease, Humans, Insulin-Secreting Cells, Male, Middle Aged, Polymorphism, Single Nucleotide, Potassium Channels, Inwardly Rectifying",
author = "Koji Okamoto and Naoko Iwasaki and Chisa Nishimura and Kent Doi and Eisei Noiri and Shinko Nakamura and Miho Takizawa and Makiko Ogata and Risa Fujimaki and Niels Grarup and Charlotta Pisinger and Knut Borch-Johnsen and Torsten Lauritzen and Annelli Sandbaek and Torben Hansen and Kazuki Yasuda and Haruhiko Osawa and Kishio Nanjo and Takashi Kadowaki and Masato Kasuga and Oluf Pedersen and Toshiro Fujita and Naoyuki Kamatani and Yasuhiko Iwamoto and Katsushi Tokunaga",
note = "2010 The American Society of Human Genetics. Published by Elsevier Inc.",
year = "2010",
doi = "10.1016/j.ajhg.2009.12.009",
language = "English",
volume = "86",
pages = "54--64",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "1",

}

RIS

TY - JOUR

T1 - Identification of KCNJ15 as a susceptibility gene in Asian patients with type 2 diabetes mellitus

AU - Okamoto, Koji

AU - Iwasaki, Naoko

AU - Nishimura, Chisa

AU - Doi, Kent

AU - Noiri, Eisei

AU - Nakamura, Shinko

AU - Takizawa, Miho

AU - Ogata, Makiko

AU - Fujimaki, Risa

AU - Grarup, Niels

AU - Pisinger, Charlotta

AU - Borch-Johnsen, Knut

AU - Lauritzen, Torsten

AU - Sandbaek, Annelli

AU - Hansen, Torben

AU - Yasuda, Kazuki

AU - Osawa, Haruhiko

AU - Nanjo, Kishio

AU - Kadowaki, Takashi

AU - Kasuga, Masato

AU - Pedersen, Oluf

AU - Fujita, Toshiro

AU - Kamatani, Naoyuki

AU - Iwamoto, Yasuhiko

AU - Tokunaga, Katsushi

N1 - 2010 The American Society of Human Genetics. Published by Elsevier Inc.

PY - 2010

Y1 - 2010

N2 - Recent advances in genome research have enabled the identification of new genomic variations that are associated with type 2 diabetes mellitus (T2DM). Via fine mapping of SNPs in a candidate region of chromosome 21q, the current study identifies potassium inwardly-rectifying channel, subfamily J, member 15 (KCNJ15) as a new T2DM susceptibility gene. KCNJ15 is expressed in the beta cell of the pancreas, and a synonymous SNP, rs3746876, in exon 4 (C566T) of this gene, with T allele frequency among control subjects of 3.1%, showed a significant association with T2DM affecting lean individuals in three independent Japanese sample sets (p = 2.5 x 10(-7), odds ratio [OR] = 2.54, 95% confidence interval [CI] = 1.76-3.67) and with unstratified T2DM (p = 6.7 x 10(-6), OR = 1.76, 95% CI = 1.37-2.25). The diabetes risk allele frequency was, however, very low among Europeans in whom no association between this variant and T2DM could be shown. Functional analysis in human embryonic kidney 293 cells demonstrated that the risk allele of the synonymous SNP in exon 4 increased KCNJ15 expression via increased mRNA stability, which resulted in the higher expression of protein as compared to that of the nonrisk allele. We also showed that KCNJ15 is expressed in human pancreatic beta cells. In conclusion, we demonstrated a significant association between a synonymous variant in KCNJ15 and T2DM in lean Japanese patients with T2DM, suggesting that KCNJ15 is a previously unreported susceptibility gene for T2DM among Asians.

AB - Recent advances in genome research have enabled the identification of new genomic variations that are associated with type 2 diabetes mellitus (T2DM). Via fine mapping of SNPs in a candidate region of chromosome 21q, the current study identifies potassium inwardly-rectifying channel, subfamily J, member 15 (KCNJ15) as a new T2DM susceptibility gene. KCNJ15 is expressed in the beta cell of the pancreas, and a synonymous SNP, rs3746876, in exon 4 (C566T) of this gene, with T allele frequency among control subjects of 3.1%, showed a significant association with T2DM affecting lean individuals in three independent Japanese sample sets (p = 2.5 x 10(-7), odds ratio [OR] = 2.54, 95% confidence interval [CI] = 1.76-3.67) and with unstratified T2DM (p = 6.7 x 10(-6), OR = 1.76, 95% CI = 1.37-2.25). The diabetes risk allele frequency was, however, very low among Europeans in whom no association between this variant and T2DM could be shown. Functional analysis in human embryonic kidney 293 cells demonstrated that the risk allele of the synonymous SNP in exon 4 increased KCNJ15 expression via increased mRNA stability, which resulted in the higher expression of protein as compared to that of the nonrisk allele. We also showed that KCNJ15 is expressed in human pancreatic beta cells. In conclusion, we demonstrated a significant association between a synonymous variant in KCNJ15 and T2DM in lean Japanese patients with T2DM, suggesting that KCNJ15 is a previously unreported susceptibility gene for T2DM among Asians.

KW - Adult

KW - Aged

KW - Asian Continental Ancestry Group

KW - Case-Control Studies

KW - Chromosomes, Human, Pair 21

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Genetic Predisposition to Disease

KW - Humans

KW - Insulin-Secreting Cells

KW - Male

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Potassium Channels, Inwardly Rectifying

U2 - 10.1016/j.ajhg.2009.12.009

DO - 10.1016/j.ajhg.2009.12.009

M3 - Journal article

C2 - 20085713

VL - 86

SP - 54

EP - 64

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 1

ER -

ID: 38335182