Molecular Biology Reports

, Volume 39, Issue 1, pp 645–659 | Cite as

Association between KCNJ11 gene polymorphisms and risk of type 2 diabetes mellitus in East Asian populations: a meta-analysis in 42,573 individuals

  • Lijuan Yang
  • Xianghai Zhou
  • Yingying Luo
  • Xiuqin Sun
  • Yong Tang
  • Wulan Guo
  • Xueyao Han
  • Linong Ji
Article

Abstract

A number of studies have been performed to identify the association between potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) gene and type 2 diabetes mellitus (T2DM) in East Asian populations, with inconsistent results. The main aim of this work was to evaluate more precisely the genetic influence of KCNJ11 on T2DM in East Asian populations by means of a meta-analysis. We identified 20 articles for qualitative analysis and 16 were eligible for quantitative analysis (meta-analysis) by database searching up to May 2010. The association was assessed under different genetic models, and the pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. The allelic and genotypic contrast demonstrated that the association between KCNJ11 and T2DM was significant for rs5210. However, not all results for rs5215 and rs5218 showed significant associations. For rs5219, the combined ORs (95% CIs) for allelic contrast, dominant and recessive models contrast (with allelic frequency and genotypic distribution data) were 1.139 (1.093–1.188), 1.177 (1.099–1.259) and 1.207 (1.094–1.332), respectively (random effect model). The analysis on the most completely adjusted ORs (95% CIs) by the covariates of rs5219 all presented significant associations under different genetic models. Population-stratified analysis (Korean, Japanese and Chinese) and sensitivity analysis verified the significant results. Cumulative meta-analysis including publication time and sample size illustrated the exaggerated genetic effect in the earliest studies. Heterogeneity and publication bias were assessed. Our study verified that single nucleotide polymorphisms (SNPs) of KCNJ11 gene were significantly associated with the risk of T2DM in East Asian populations.

Keywords

KCNJ11 Polymorphisms Type 2 diabetes mellitus Meta-analysis Association 

Abbreviations

KCNJ11

Potassium inwardly-rectifying channel, subfamily J, member 11

T2DM

Type 2 diabetes mellitus

OR

Odds ratio

CI

Confidence interval

SNP

Single nucleotide polymorphism

GWAS

Genome-wide association study

KATP

ATP-sensitive K+ channel

SUR1

Sulfonylurea receptor 1

CNKI

China National Knowledge Infrastructure

MOOSE

Meta-analysis of Observation Studies in Epidemiology

HWE

Hardy–Weinberg equilibrium

R/r

Risk allele/reference allele

C–C

Case–control study

C–S

Follow-up and cross-sectional study

WHO

World Health Organization

ADA

American Diabetes Association

M/F

Male/female

PCR–RFLP

PCR–restriction fragment-length polymorphism

TaqMan

TaqMan SNP genotyping assays

M/m

Major allele/minor allele

MAF

Minor allele frequency

LD

Linkage disequilibrium

M–H

A fixed-effect model using the Mantel–Haenszel method

I-V

A fixed-effect model using the Inverse-Variance method

D+L

A random-effect model using the Der Simonian and Laird method

NS

Not stated

Notes

Acknowledgments

This study was supported by the National Basic Research Program of China (973 program, 2006CB503900) and the National High Technology Research and Development Program of China (863 program, 2006AA02A409).

Supplementary material

11033_2011_782_MOESM1_ESM.doc (174 kb)
Supplementary material 1 (DOC 174 kb)
11033_2011_782_MOESM2_ESM.doc (58 kb)
Supplementary material 2 (DOC 57 kb)

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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Lijuan Yang
    • 1
  • Xianghai Zhou
    • 1
  • Yingying Luo
    • 1
  • Xiuqin Sun
    • 1
  • Yong Tang
    • 1
  • Wulan Guo
    • 1
  • Xueyao Han
    • 1
  • Linong Ji
    • 1
  1. 1.Department of Endocrinology and MetabolismPeking University People’s HospitalBeijingChina

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