PMID- 20085713
OWN - NLM
STAT- MEDLINE
DCOM- 20100225
LR  - 20240317
IS  - 1537-6605 (Electronic)
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 86
IP  - 1
DP  - 2010 Jan
TI  - Identification of KCNJ15 as a susceptibility gene in Asian patients with type 2 
      diabetes mellitus.
PG  - 54-64
LID - 10.1016/j.ajhg.2009.12.009 [doi]
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.
CI  - 2010 The American Society of Human Genetics. Published by Elsevier Inc.
FAU - Okamoto, Koji
AU  - Okamoto K
AD  - Department of Human Genetics, Graduate School of Tokyo University, Japan.
FAU - Iwasaki, Naoko
AU  - Iwasaki N
FAU - Nishimura, Chisa
AU  - Nishimura C
FAU - Doi, Kent
AU  - Doi K
FAU - Noiri, Eisei
AU  - Noiri E
FAU - Nakamura, Shinko
AU  - Nakamura S
FAU - Takizawa, Miho
AU  - Takizawa M
FAU - Ogata, Makiko
AU  - Ogata M
FAU - Fujimaki, Risa
AU  - Fujimaki R
FAU - Grarup, Niels
AU  - Grarup N
FAU - Pisinger, Charlotta
AU  - Pisinger C
FAU - Borch-Johnsen, Knut
AU  - Borch-Johnsen K
FAU - Lauritzen, Torsten
AU  - Lauritzen T
FAU - Sandbaek, Annelli
AU  - Sandbaek A
FAU - Hansen, Torben
AU  - Hansen T
FAU - Yasuda, Kazuki
AU  - Yasuda K
FAU - Osawa, Haruhiko
AU  - Osawa H
FAU - Nanjo, Kishio
AU  - Nanjo K
FAU - Kadowaki, Takashi
AU  - Kadowaki T
FAU - Kasuga, Masato
AU  - Kasuga M
FAU - Pedersen, Oluf
AU  - Pedersen O
FAU - Fujita, Toshiro
AU  - Fujita T
FAU - Kamatani, Naoyuki
AU  - Kamatani N
FAU - Iwamoto, Yasuhiko
AU  - Iwamoto Y
FAU - Tokunaga, Katsushi
AU  - Tokunaga K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (KCNJ15 protein, human)
RN  - 0 (Potassium Channels, Inwardly Rectifying)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Asian People
MH  - Case-Control Studies
MH  - Chromosomes, Human, Pair 21
MH  - Diabetes Mellitus, Type 2/*ethnology/*genetics
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - Humans
MH  - Insulin-Secreting Cells/metabolism
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide
MH  - Potassium Channels, Inwardly Rectifying/*genetics/*physiology
PMC - PMC2801752
EDAT- 2010/01/21 06:00
MHDA- 2010/02/26 06:00
PMCR- 2010/07/08
CRDT- 2010/01/21 06:00
PHST- 2009/09/04 00:00 [received]
PHST- 2009/11/07 00:00 [revised]
PHST- 2009/12/04 00:00 [accepted]
PHST- 2010/01/21 06:00 [entrez]
PHST- 2010/01/21 06:00 [pubmed]
PHST- 2010/02/26 06:00 [medline]
PHST- 2010/07/08 00:00 [pmc-release]
AID - S0002-9297(09)00570-9 [pii]
AID - AJHG538 [pii]
AID - 10.1016/j.ajhg.2009.12.009 [doi]
PST - ppublish
SO  - Am J Hum Genet. 2010 Jan;86(1):54-64. doi: 10.1016/j.ajhg.2009.12.009.