<i><scp>KCNQ</scp>1</i> rs2237892 C→T gene polymorphism and type 2 diabetes mellitus in the Asian population: a meta‐analysis of 15,736 patients

Li, Yanyan; Wang, Xiangming; Lu, Xiyi

doi:10.1111/jcmm.12185

Cited by 22 publications

(19 citation statements)

References 24 publications

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“…To exclude the impact of OATP1B and CYP2C8 genetic polymorphisms on the response to repaglinide, participants with the same OATP1B1 521TT and CYP2C8*3 139 Arg genotypes but different KCNQ1 rs2237892 genotypes were randomly selected. Consistent with the results in Korean and Malaysian subgroups, we determined in our study that the frequency of the C allele in KCNQ1 rs2237892 was significantly higher in patients with T2DM than in healthy controls24 (Table 2). With respect to repaglinide efficacy, patients with the CC genotype exhibited lower IR at baseline (HOMA-IR = 4.24) than individuals with the CT/TT (HOMA-IR = 5.67) genotypes (P = 0.046) (Table 3).…”

Section: Discussionsupporting

confidence: 89%

A variation in KCNQ1 gene is associated with repaglinide efficacy on insulin resistance in Chinese Type 2 Diabetes Mellitus Patients

Zhou

Zhu

Bao

et al. 2016

Sci Rep

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Repaglinide is an insulin secretagogue that often exhibits considerable interindividual variability in therapeutic efficacy. The current study was designed to investigate the impact of KCNQ1 genetic polymorphism on the efficacy of repaglinide and furthermore to identify the potential mechanism of action in patients with type 2 diabetes. A total of 305 patients and 200 healthy subjects were genotyped for the KCNQ1 rs2237892 polymorphism, and 82 patients with T2DM were randomized for the oral administration of repaglinide for 8 weeks. HepG2 cells were incubated with repaglinide in the absence or presence of a KCNQ1 inhibitor or the pcDNA3.1-hKCNQ1 plasmid, after which the levels of Akt, IRS-2 and PI(3)K were determined. Our data showed that repaglinide significantly decreased HOMA-IR in patients with T2DM. Furthermore, the level of HOMA-IR was significantly reduced in those patients with CT or TT genotypes than CC homozygotes. The KCNQ1 inhibitor enhanced repaglinide efficacy on insulin resistance, with IRS-2/PI(3)K/Akt signaling being up-regulated markedly. As in our clinical experiment, these data strongly suggest that KCNQ1 genetic polymorphism influences repaglinide response due to the pivotal role of KCNQ1 in regulating insulin resistance through the IRS-2/PI(3)K/Akt signaling pathway. This study was registered in the Chinese Clinical Trial Register on May 14, 2013. (No. ChiCTR-CCC13003536).

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Section: Discussionsupporting

confidence: 89%

A variation in KCNQ1 gene is associated with repaglinide efficacy on insulin resistance in Chinese Type 2 Diabetes Mellitus Patients

Zhou

Zhu

Bao

et al. 2016

Sci Rep

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“…There was no statistically significant association in the Caucasian subgroup in this meta-analysis, most likely because our relatively strict selection criteria-enough genotype information was required-did not allow the study to be included. Another study by Li et al [64], with 9 studies included (6707 cases and 8129 controls), was only performed for rs2237892. They found a significant association between KCNQ1 rs2237892 T polymorphism and T2DM in the Asian population under the allelic (OR = 1:350; P < 0:001), recessive (OR = 0:650; P < 0:001), dominant (OR = 1:450; P < 0:001), and additive genetic models (OR = 1:346; P < 0:001).…”

Section: Discussionmentioning

confidence: 99%

Associations ofKCNQ1Polymorphisms with the Risk of Type 2 Diabetes Mellitus: An Updated Meta-Analysis with Trial Sequential Analysis

Liao

Zeng³

et al. 2020

Journal of Diabetes Research

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Background. Previous studies have examined the role of the KQT-like subfamily Q member1 (KCNQ1) gene polymorphisms on the risk of type 2 diabetes mellitus (T2DM), but the findings are inconclusive. Objective. To examine the association between the KCNQ1 gene polymorphisms and the risk of T2DM using an updated meta-analysis with an almost tripled number of studies. Methods. Five electronic databases, such as PubMed and Embase, were searched thoroughly for relevant studies on the associations between seven most studied KCNQ1 gene polymorphisms, including rs2237892, rs2237897, rs2237895, rs2283228, rs231362, rs151290, and rs2074196, and T2DM risk up to September 14, 2019. The summary odds ratios (ORs) with their 95% confidence intervals (CIs) were applied to assess the strength of associations in the random-effects models. We used the trial sequential analysis (TSA) to measure the robustness of the evidence. Results. 49 publications including 55 case-control studies (68,378 cases and 66,673 controls) were finally enrolled. In overall analyses, generally, increased T2DM risk was detected for rs2237892, rs2237895, rs2283228, rs151290, and rs2074196, but not for rs231362 under all genetic models. The ORs and 95% CIs for allelic comparison were 1.23 (1.14-1.33) for rs2237892, 1.21 (1.16-1.27) for rs2237895, 1.27 (1.11-1.46) for rs2237897, 1.25 (1.09-1.42) for rs2283228, 1.14 (1.03-1.27) for rs151290, 1.31 (1.23-1.39) for rs2074196, and 1.16 (0.83, 1.61) for rs231362. Stratified analyses showed that associations for rs2237892, rs2237895, rs2283228, and rs151290 were more evident among Asians than Caucasians. TSA demonstrated that the evidence was sufficient for all polymorphisms in this study. The genotypes of the three SNPs (rs2237892, rs2283228, and rs231362) were significantly correlated with altered KCNQ1 gene expression. Conclusion. This meta-analysis suggested that KCNQ1 gene polymorphisms (rs2237892, rs2283228, rs2237895, rs151290, and rs2074196) might be the susceptible factors for T2DM, especially among Asian population.

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“…At least 57 genes located on 16 different chromosomes and 136 single nucleotide polymorphisms (SNPs) regulating pathways related to insulin secretion, resistance, signaling, and β‐cell dysfunction (Cui et al, ; Li et al, ; Tsai et al, ) have been reported to affect the pathogenesis of T2DM. Among these, KCNQ1 has been found to contribute to the genetic susceptibility of T2DM in the European and Japanese populations, as well as in other Asian populations (Li, Wang, & Lu, ; Tsai et al, ; Unoki et al, ; Yasuda et al, ). KCNQ1 encodes a protein of the potassium voltage‐gated channel subfamily that is expressed in insulin secreting cells (Ullrich et al, ); notably, the KCNQ1 blocking agent 293B has been found to stimulate insulin secretion (Ullrich et al, ).…”

Section: Introductionmentioning

confidence: 99%

KCNQ1 variants associate with hypertension in type 2 diabetes and affect smooth muscle contractility in vitro

Huang

Liu

et al. 2017

Journal Cellular Physiology

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KCNQ1 encodes a potassium voltage-gated channel and represents a susceptibility locus for type 2 diabetes mellitus (T2DM). Here, we explored the association between KCNQ1 polymorphisms and hypertension risk in individuals with T2DM, as well as the role of KCNQ1 in vascular smooth muscle cell contraction in vitro. To investigate the relationship between KCNQ1 and the risk of developing hypertension in patients with T2DM, we divided the T2DM cohort into hypertension (n = 452) and non-hypertension (n = 541) groups. The Mann-Whitney U test, chi-square test, and multivariate regression analyses were used to assess the clinical characteristics and genotypic frequencies. In vitro studies utilized the rat aortic smooth muscle A10 cell line. Patients in the hypertension group were significantly older at the time of enrollment and had higher levels of body mass index, waist-to-hip ratio, and triglyceride than those in the non-hypertension group. The KCNQ1 rs3864884 and rs12576239 genetic variants were associated with hypertension in T2DM. KCNQ1 expression was lower in the individuals with the CC versus the CT and TT genotypes. Smooth muscle cell contractility was inhibited by treatment with a KCNQ1 inhibitor. These results suggest that KCNQ1 might be associated with hypertension in individuals with T2DM.

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

Cited by 22 publications

References 24 publications

A variation in KCNQ1 gene is associated with repaglinide efficacy on insulin resistance in Chinese Type 2 Diabetes Mellitus Patients

A variation in KCNQ1 gene is associated with repaglinide efficacy on insulin resistance in Chinese Type 2 Diabetes Mellitus Patients

Associations ofKCNQ1Polymorphisms with the Risk of Type 2 Diabetes Mellitus: An Updated Meta-Analysis with Trial Sequential Analysis

KCNQ1 variants associate with hypertension in type 2 diabetes and affect smooth muscle contractility in vitro

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