Meta-analysis of the effect of KCNQ1 gene polymorphism on the risk of type 2 diabetes

Abstract

The potassium voltage-gated channel, KQT-like subfamily member 1 (KCNQ1) is a member of 11 mammalian Kv channel families that plays a key role for the repolarization of the cardiac action potential as well as water and salt transport. 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, rs2237895, rs2237897, rs2283228, and rs231362 polymorphism in KCNQ1 has been implicated in T2D risk. However, studies on the association between these polymorphism and T2D remain conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 114,140 patients and 167,322 controls from 30 published case-control studies was performed. Overall, significantly elevated T2D risk was associated with rs2237892, rs2237895, rs2237897, rs2283228, and rs231362 risk allele when all studies were pooled into the meta-analysis. In the subgroup analysis by ethnicity, sample size, and Hardy-Weinberg equilibrium status of controls, significantly increased risks were found for these polymorphisms. In conclusion, this meta-analysis suggests that rs2237892, rs2237895, rs2237897, rs2283228, and rs231362 polymorphisms in KCNQ1 are associated with elevated T2D risk.

Correlation between KCNQ1 and KCNJ11 gene polymorphisms and type 2 and post-transplant diabetes mellitus in the Asian Indian population

“…A meta-analysis study by Liu et al 31 demonstrated a positive association between the KCNQ1 rs2283228 polymorphism and T2DM. The rs2283228 variant, previously associated with T2DM in European (Danish), but not in Chinese (Singaporean) and Arab (Tunisian) populations, 21 , 32 , 33 was associated with T2DM in Asian Indians.…”

“…The KCNQ1 gene encodes the pore-forming subunit of a voltage-gated potassium channel that plays a key role in the repolarization of the cardiac-action potential as well as in the transport of water and salts in epithelial tissues. 31 KCNQ1 is expressed in pancreatic β-cells, and KCNJ11 plays a strategic role in insulin secretion by glucose-stimulated pancreatic β-cells.…”

KCNQ1 rs2237892 C→T gene polymorphism and type 2 diabetes mellitus in the Asian population: a meta‐analysis of 15,736 patients

“… and Liu et al . also performed two meta‐analyses on the relationship between KCNQ1 rs2237892 C→T gene polymorphism and T2DM afterwards. Although they obtained positive results, the number of genotypes in the aforementioned manuscripts could not be retrieved yet and neither of their conclusions was credible.…”

“…Moreover, with regard to the study of Tan et al [17] involving meta-analysis, only the allelic genetic model is used and the credibility of their results is doubtful. In addition, Sun et al [18] and Liu et al [19] also performed two meta-analyses on the relationship between KCNQ1 rs2237892 C? T gene polymorphism and T2DM afterwards.…”

Increased burden of rare deleterious variants of the KCNQ1 gene in patients with large‑vessel ischemic stroke

“…Because of the demonstrated deleterious properties of the investigated variants, it should be also considered that the stroke patients in the study may have suffered from an ischemic stroke secondary to a congenital disorder. Whether KCNQ1 variants are disease-associated with ischemic stroke (possibly via platelet function) or disease-causing for congenital QT syndrome (with reportedly higher incidence of ischemic stroke is one of the questions which should be clarified in the future investigations (41). Moreover, in one of the largest to date GWAS on platelet function, KCNQ1 locus was discovered to contribute to platelet function variability (19,20).…”