Association between KCNQ1 genetic variants and obesity in Chinese patients with type 2 diabetes

Wang, Yu; Ma, Rong; Hu, Cheng; So, Wing‐Yee; Zhang, R.; Wang, C.; Tam, Claudia H. T.; Ho, Janice; Lu, Jingyi; Fan, Jian‐Gao; Tang, Shanshan; Ng, Maggie; Bao, Yuqian; Xiang, Kun–san; Jia, Weiping; Chan, Juliana C.N.

doi:10.1007/s00125-012-2636-8

Cited by 20 publications

(25 citation statements)

References 10 publications

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“…Variant allele T of rs2237892 was associated with a higher prevalence of overwight, but was with a lower prevalence of diabetes in our study, which was consistent with previous studies [31],[33]–[35]. Biologically, KCNQ1 is a gene encoding the poreforming subunit of a voltage-gated K+ channel that plays a key role in the repolarization of the cardiac action potential as well as water and salt transportation in the beta cells [19],[32],[36]. KV-channel knock-out in rat islets as well as pharmacological inhibition of KV-channels in rat beta cells have been reported to enhance glucose-stimulated insulin secretion [37]–[39].…”

Section: Discussionsupporting

confidence: 91%

“…In the study by Xia Li et al , rs11705701, a SNP in strong LD with rs4402960, was identified to be associated with percent body fat in Mexican Americans [30]. In addition, SNP rs2237892 located within gene KCNQ1 was found to be associated with both overweight and obesity and diabetes at first [19,[31],[32]. Variant allele T of rs2237892 was associated with a higher prevalence of overwight, but was with a lower prevalence of diabetes in our study, which was consistent with previous studies [31],[33]–[35].…”

Section: Discussionmentioning

confidence: 99%

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Genetic Association Study with Metabolic Syndrome and Metabolic-Related Traits in a Cross-Sectional Sample and a 10-Year Longitudinal Sample of Chinese Elderly Population

Yang

Liu

et al. 2014

PLoS ONE

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BackgroundThe metabolic syndrome (MetS) has been known as partly heritable, while the number of genetic studies on MetS and metabolic-related traits among Chinese elderly was limited.MethodsA cross-sectional analysis was performed among 2 014 aged participants from September 2009 to June 2010 in Beijing, China. An additional longitudinal study was carried out among the same study population from 2001 to 2010. Biochemical profile and anthropometric parameters of all the participants were measured. The associations of 23 SNPs located within 17 candidate genes (MTHFR, PPARγ, LPL, INSIG, TCF7L2, FTO, KCNJ11, JAZF1, CDKN2A/B, ADIPOQ, WFS1, CDKAL1, IGF2BP2, KCNQ1, MTNR1B, IRS1, ACE) with overweight and obesity, diabetes, metabolic phenotypes, and MetS were examined in both studies.ResultsIn this Chinese elderly population, prevalence of overweight, central obesity, diabetes, dyslipidemia, hypertension, and MetS were 48.3%, 71.0%, 32.4%, 75.7%, 68.3% and 54.5%, respectively. In the cross-sectional analyses, no SNP was found to be associated with MetS. Genotype TT of SNP rs4402960 within the gene IGF2BP2 was associated with overweight (odds ratio (OR) = 0.479, 95% confidence interval (CI): 0.316-0.724, p = 0.001) and genotype CA of SNP rs1801131 within the gene MTHFR was associated with hypertension (OR = 1.560, 95% CI: 1.194–2.240, p = 0.001). However, these associations were not observed in the longitudinal analyses.ConclusionsThe associations of SNP rs4402960 with overweight as well as the association of SNP rs1801131 with hypertension were found to be statistically significant. No SNP was identified to be associated with MetS in our study with statistical significance.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Genetic Association Study with Metabolic Syndrome and Metabolic-Related Traits in a Cross-Sectional Sample and a 10-Year Longitudinal Sample of Chinese Elderly Population

Yang

Liu

et al. 2014

PLoS ONE

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“…The association of rs2237892 polymorphism and rising T2DM incident risk proved former study result [2,4,[7][8][9][11][12][13][14][15][16][17][21][22][23][24]27,[29][30][31]36,[39][40][41][42][43][44][45][46]. East Asian, Southeast Asian and other region`s subgroup analysis also show the association still stable（OR=1.…”

Section: Main Discoversmentioning

confidence: 61%

“…This meta-analysis about rs2237892 polymorphism and T2DM involve 40 article [2,[35][36][37][38][39][40][42][43][44][45][46], contain 52 study data set, 61757 T2DM patient and 59078 control(only calculate once in every study`s case and control group). The association of rs2237892 polymorphism and rising T2DM incident risk proved former study result [2,4,[7][8][9][11][12][13][14][15][16][17][21][22][23][24]27,[29][30][31]36,[39][40][41][42][43][44][45][46].…”

Section: Main Discoversmentioning

confidence: 99%

Association Between KCNQ1 Gene Polymorphism and Type 2 Diabetes Mellitus: Evidence from Meta-analysis

Qin¹,

Dong²,

Jiang³

et al. 2018

dtbh

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Abstract.A meta-analysis is performed by Stata software for evaluating the relationship between rs2237892， rs2237895 polymorphism in KCNQ1 and type2 diabetes mellitus(T2DM). The Forest plot is estimate the association between T2DM and KCNQ1 Gene polymorphism, and the heterogeneity, Funnel plot as well as Egger's regression tests for publishing bias are assessed through Stata12.0 software. In our meta-analysis, there are 40 articles related rs2237892 included, 61757 T2DM patients and 59078 controls involved; 21 articles on rs2237985 is selected, including 42594 T2DM patients and 45306 controls. The distribution frequency of C allele of rs2237892 and rs2237895 in T2DM are obvious higher than control, combine OR （95%CI） are 1.29(1.27-1.32) and 1.24(1.22-1.27)， showing remarkable statistical significance (z=24.29, P ＜ 0.001; z=20.14, P ＜ 0.001). The rs2237892 and rs2237895 polymorphism in KCNQ1 would increase risk of T2DM.

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“…Recent studies have linked the voltage-gated potassium channel KQTlike sub-family, member 1 gene (KCNQ1) to T2DM susceptibility in East Asians [12,13] and to obesity in China [14] . Specifically, KCNQ1 channels might play a role in the regulation of insulin secretion and participate in the regulation of cell volume, which is critically important for the regulation of metabolism by insulin [13,[15][16][17][18] .…”

Section: Abcc8 Kcnj11 Cyp2c9 Tcf7l2 Pparg Irs1 and Nos1apmentioning

confidence: 99%

Polymorphisms of the KCNQ1 gene are associated with the therapeutic responses of sulfonylureas in Chinese patients with type 2 diabetes

Tang

Jiang

et al. 2016

Acta Pharmacol Sin

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KCNQ1 channel is a member of the voltage-gated potassium channel KQT-like subfamily. The KCNQ1 gene has recently been identified as a susceptibility locus for type 2 diabetes mellitus (T2DM). In the present study, we examined the effects of KCNQ1 variants on the therapeutic response to modified-release gliclazide (gliclazide MR) treatment in Chinese patients newly diagnosed with T2DM. A total of 100 newly diagnosed T2DM patients without a history of any anti-diabetic medications were treated with gliclazide MR for 16 weeks, but 91 patients completed the entire study. The anthropometric parameters were determined at baseline and at the final visit, while clinical laboratory tests were performed at baseline and on weeks 2, 4, 6, 12, 16. Two SNPs, rs2237892 and rs2237895, in the region of the KCNQ1 gene were genotyped in all the participants. All calculations and statistical analyses were conducted using SPSS. The rs2237892 TT homozygotes exhibited significantly higher 2-h glucose levels at baseline (P<0.05) and a lower cumulative attainment rate of the target 2-h glucose level (P log-rank =0.020) than the C allele carriers. Patients with greater numbers of rs2237892 T alleles exhibited larger augmentations (Δ) in the 2-h glucose levels (P=0.027); and patients with the rs2237892 TT genotype exhibited a higher Δ homeostasis model assessment of β-cell function (HOMA-β) than CC and CT genotype carriers (P=0.021 and P=0.043, respectively). Moreover, the rs2237895 C allele was associated with a greater decrement in Δ glycated hemoglobin (HbA1c) (P=0.024); and patients with the CC genotype exhibited greater variance than those with the AA and AC genotypes (P=0.005 and 0.021, respectively). Compared with the C allele, the odds ratio for treatment success among carriers of the rs2237892 T allele was 2.533 (P=0.007); and the rs2237895 C allele was associated with a 2.360-fold decrease in HbA1c compared with the A allele (P=0.009). KCNQ1 polymorphisms are associated with gliclazide MR efficacy in Chinese patients with type 2 diabetes.

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Association between KCNQ1 genetic variants and obesity in Chinese patients with type 2 diabetes

Cited by 20 publications

References 10 publications

Genetic Association Study with Metabolic Syndrome and Metabolic-Related Traits in a Cross-Sectional Sample and a 10-Year Longitudinal Sample of Chinese Elderly Population

Genetic Association Study with Metabolic Syndrome and Metabolic-Related Traits in a Cross-Sectional Sample and a 10-Year Longitudinal Sample of Chinese Elderly Population

Association Between KCNQ1 Gene Polymorphism and Type 2 Diabetes Mellitus: Evidence from Meta-analysis

Polymorphisms of the KCNQ1 gene are associated with the therapeutic responses of sulfonylureas in Chinese patients with type 2 diabetes

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