Abstract
To clarify the role of potassium inwardly-rectifying-channel, subfamily-J, member 11 (KCNJ11) variation in susceptibility to type 2 diabetes (T2D), we performed a systematic meta-analysis to investigate the association between the KCNJ11 E23K polymorphism (rs5219) and the T2D in different genetic models. Databases including PubMed, Medline, EMBASE, and ISI Web of Science were searched to identify relevant studies. A total of 48 published studies involving 56,349 T2D cases, 81,800 controls, and 483 family trios were included in this meta-analysis. Overall, the E23K polymorphism was significantly associated with increased T2D risk with per-allele odds ratio (OR) of 1.12 (95% CI: 1.09–1.16; P<10−5). The summary OR for T2D was 1.09 (95% CI: 1.03–1.14; P<10−5), and 1.26 (95% CI: 1.17–1.35; P<10−5), for heterozygous and homozygous, respectively. Similar results were also detected under dominant and recessive genetic models. When stratified by ethnicity, significantly increased risks were found for the polymorphism in Caucasians and East Asians. However, no such associations were detected among Indian and other ethnic populations. Significant associations were also observed in the stratified analyses according to different mean BMI of cases and sample size. Although significant between study heterogeneity was identified, meta-regression analysis suggested that the BMI of controls significantly correlated with the magnitude of the genetic effect. The current meta-analysis demonstrated that a modest but statistically significant effect of the 23K allele of rs5219 polymorphism in susceptibility to T2D. But the contribution of its genetic variants to the epidemic of T2D in Indian and other ethnic populations appears to be relatively low.
Highlights
Type 2 diabetes (T2D) is a complex metabolic disease resulting from reduced insulin secretion and peripheral insulin resistance
The overall result showed that the 23K allele of rs5219 polymorphism was significantly associated with elevated T2D risk with per-allele odds ratio (OR) of 1.12
When studies were stratified for ethnic populations, significant associations were observed among East Asian and Caucasian populations with per-allele OR of 1.13 and of 1.12 respectively
Summary
Type 2 diabetes (T2D) is a complex metabolic disease resulting from reduced insulin secretion and peripheral insulin resistance. The KATP channel is a hetero-octamer of K+ inward rectifier Kir6.2 (KCNJ11) and regulatory sulfonylurea receptor SUR1 subunits (ABCC8) [2]. Mutations in both KCNJ11 and ABCC8 cause neonatal diabetes and congenital hyper-insulinemia in humans [3,4]. Inconsistent results have appeared in the literature Such inconsistence may be due to chance, insufficient power of limited sample size, or bias in study design (e.g., inappropriate control selection). These disparate findings may reflect ethnic diversity (e.g., population stratification) or phenotypic heterogeneity. We present the most comprehensive meta-analysis for the effects of E23K polymorphism of KCNJ11 on T2D risk
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