Abstract
BackgroundKCNQ1 (potassium voltage-gated channel KQT-like sub-family, member 1) encodes a pore-forming subunit of a voltage-gated K+ channel (KvLQT1) that plays a key role for the repolarization of the cardiac action potential as well as water and salt transport in epithelial tissues. Recently, genome-wide association studies have identified KCNQ1 as a type 2 diabetes (T2D) susceptibility gene in populations of Asian descent. After that, a number of studies reported that the rs2237892 and rs2237895 polymorphism in KCNQ1 has been implicated in T2D risk. However, studies on the association between these polymorphism and T2D remain conflicting. To investigate this inconsistency, we performed this meta-analysis.MethodsDatabases including Pubmed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI) were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Potential sources of heterogeneity were also assessed by subgroup analysis and meta-regression.ResultsA total of 25 articles involving 70,577 T2D cases and 99,068 controls were included. Overall, the summary odds ratio of C allele for T2D was 1.32 (95% CI 1.26–1.38; P<10−5) and 1.24 (95% CI: 1.20–1.29; P<10−5) for KCNQ1 rs2237892 and rs2237895 polymorphisms, respectively. Significant results were also observed using co-dominant, dominant and recessive genetic models. After stratifying by ethnicity, sample size, and diagnostic criteria, significant associations were also obtained.ConclusionsThis meta-analysis suggests that the rs2237892 and rs2237895 polymorphisms in KCNQ1 are associated with elevated type 2 diabetes susceptibility.
Highlights
Type 2 diabetes (T2D) is a complex metabolic disorder characterized by variable degrees of insulin resistance, impaired insulin secretion and elevated blood glucose
2012 on T2D and polymorphisms in the KCNQ1 gene were identified through a search of PubMed, Web of Science, EMBASE and China National Knowledge Infrastructure (CNKI) (Chinese National Knowledge Infrastructure) with keywords ‘‘KQT-like subfamily, member 1’’, ‘‘KCNQ1’’, ‘‘type 2 diabetes mellitus’’, ‘‘type 2 diabetes’’, ‘‘T2D’’, ‘‘T2DM’’
Eligible studies had to meet all of the following criteria: (a) should have been published in peer-reviewed journal; (b) were independent association studies investigating polymorphism with T2D using original data; (c) should have presented sufficient data to calculate the odds ratio (OR) with confidence interval (CI) and p value, and (d) should have described the genotyping method, equipment, and protocols used or provided reference to them
Summary
Type 2 diabetes (T2D) is a complex metabolic disorder characterized by variable degrees of insulin resistance, impaired insulin secretion and elevated blood glucose. It has become a global major health problem showing worldwide increasing prevalence with an estimated 300 million people predicted to develop the disease by 2025 [1]. Spectacular advance was made in identifying susceptible genes involved in T2D through genome-wide association strategy (GWAS) [2]. Genome-wide association studies have identified KCNQ1 as a type 2 diabetes (T2D) susceptibility gene in populations of Asian descent. Studies on the association between these polymorphism and T2D remain conflicting.
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