Genetic Variation in <i>KCNQ1</i> Associates With Fasting Glucose andβ-Cell Function

Tan, Jonathan T.; Nurbaya, Siti; Gardner, Daphne; Ye, Sandra; Tai, E. Shyong; Ng, Daniel P.K.

doi:10.2337/db08-1138

Cited by 81 publications

(92 citation statements)

References 15 publications

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“…In previous studies conducted in East Asian populations, the variant rs2237892 from intron 15 of the KCNQ1 gene was the SNP most frequently associated with T2DM and altered fasting insulin levels. 11,24 Additionally, several studies reported that the KCNQ1 gene was related to diabetes in the Korean population. [19][20][21] Most of these studies used a case subject-control subject design that tended to overestimate the risk of an SNP because case subjects and control subjects usually represented two extremes of the distribution of glucose tolerance.…”

Section: Discussionmentioning

confidence: 99%

Impact of common type 2 diabetes risk gene variants on future type 2 diabetes in the non-diabetic population in Korea

Park

Lee

et al. 2012

J Hum Genet

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We prospectively examined the association between type 2 diabetes mellitus (T2DM) progression and common T2DM-risk gene variants in 870 non-diabetic participants in a Chungju Metabolic Disease Cohort Study in Korea. We genotyped the following six single nucleotide polymorphisms (SNPs): KCNQ1 (potassium voltage-gated channel, KQT-like subfamily member 1) rs2237892, CDKAL1 (regulatory subunit-associated protein 1-like 1) rs7554840, CDKN2A/B (cyclin-dependent kinase inhibitor 2A/B) rs1081161, SCL30A8 (solute carrier family 30 member 8 gene) rs13266634, TCF7L2 (transcription factor 7-like 2) rs7903146, and PPARG (peroxisome proliferator activated receptor gamma) rs1801282. Anthropometric data and metabolic parameters were obtained at baseline and year 4. Pancreatic b cell function was assessed by the homeostasis model assessment index of b cells (HOMA-b). After 4 years, 137 subjects developed T2DM (15.7%). A significant association was found in the variant of KCNQ1 rs2237892, whereas the SNPs of CDKAL1, CDKN2A/B, SCL30A8, TCF7L2 and PPARG were not associated. The C-allele carriers of KCNQ1 conferred a significantly increased risk for T2DM compared with the T/T genotype, independently of clinical risk factors (odds ratio¼2.61, 95% confidence intervals¼1.02-6.69, P¼0.04). Although no differences were observed at baseline among the KCNQ1 variants, HOMA-b levels by year 4 were significantly lower in the C-allele carriers after controlling for metabolic parameters. The genetic variations in KCNQ1 are associated with future development of T2DM in Koreans, which might be mediated by differences in insulin secretory function.

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Section: Discussionmentioning

confidence: 99%

Impact of common type 2 diabetes risk gene variants on future type 2 diabetes in the non-diabetic population in Korea

Park

Lee

et al. 2012

J Hum Genet

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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%

“…As the same we random report the result of meta-analysis. European Saif-Ali R,2011 [26] Fuu-Jen Tsai, 2010 [34] Fuu-Jen Tsai, 2010 [34] Qi QB, 2009 [38] Turki A, 2012 [20] Dai XP, 2012 [17] Tan JT, 2009 [39] H. Grallert, 2010[33] ID Been LF, 2011 [24] Hiroyuki Unoki, 2008 [3] van Vliet-Ostaptchouk JV,2012 [21] Cui LJ,2016 [5] Chen Z, 2010 [28] Odgerel Z, 2012 [15] …”

Section: Association Of Rs2237892 Polymorphism With T2dmentioning

confidence: 99%

“…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%

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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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“…Both in vitro systems and in vivo studies in the knockout mice and humans, [60][61][62][63] have implicated ZnT8 in the development of T2D and are closely related to insulin synthesis and/or secretion. Another extensively studied susceptibility gene is KCNQ1, which was also reported to be highly related to cell function [64,65]. Many of the T2D susceptibility genes identified by GWAS affect cell function (cell cycle regulation), and only a limited number of T2D GWAS loci are associated with insulin resistance (e.g., PPARG, FTO, IRS1 and KLF14) [34].…”

Section: New Susceptibility Genes Were Identified By Gwasmentioning

confidence: 99%

The New Perspectives on Genetic Studies of Type 2 Diabetes and Thyroid Diseases

Xu¹,

Bi²,

Cui³

et al. 2013

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Abstract:Recently, genome-wide association studies (GWAS) have led to the discovery of hundreds of susceptibility loci that are associated with complex metabolic diseases, such as type 2 diabetes and hyperthyroidism. The majority of the susceptibility loci are common across different races or populations; while some of them show ethnicity-specific distribution. Though the abundant novel susceptibility loci identified by GWAS have provided insight into biology through the discovery of new genes or pathways that were previously not known, most of them are in introns and the associated variants cumulatively explain only a small fraction of total heritability. Here we reviewed the genetic studies on the metabolic disorders, mainly type 2 diabetes and hyperthyroidism, including candidate genes-based findings and more recently the GWAS discovery; we also included the clinical relevance of these novel loci and the gene-environmental interactions. Finally, we discussed the future direction about the genetic study on the exploring of the pathogenesis of the metabolic diseases.

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Genetic Variation in KCNQ1 Associates With Fasting Glucose andβ-Cell Function

Cited by 81 publications

References 15 publications

Impact of common type 2 diabetes risk gene variants on future type 2 diabetes in the non-diabetic population in Korea

Impact of common type 2 diabetes risk gene variants on future type 2 diabetes in the non-diabetic population in Korea

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

The New Perspectives on Genetic Studies of Type 2 Diabetes and Thyroid Diseases

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