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Published in: Journal of Diabetes & Metabolic Disorders 1/2020

01-06-2020 | Diabetes | Research article

KCNQ1 common genetic variant and type 2 diabetes mellitus risk

Authors: Taraneh Erfani, Negar Sarhangi, Mahdi Afshari, Davood Abbasi, Hamid Reza Aghaei Meybodi, Mandana Hasanzad

Published in: Journal of Diabetes & Metabolic Disorders | Issue 1/2020

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Abstract

Background

Type 2 diabetes mellitus (T2DM) is a multifactorial trait that both environmental and genetic factors contribute to its pathogenesis. The most common single nucleotide polymorphism (SNP) of the potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene, rs2237892, is highly associated with the risk of T2DM. The aim of the present study was to examine any association between KCNQ1 gene rs2237892 variant and risk of T2DM in a group of Iranian patients.

Methods

Genotyping was carried out in 100 type 2 diabetic patients and 100 non-diabetic subjects using the Sanger sequencing method.

Results

The CC genotype caused more than 30% reduction in the risk of T2DM in compared with CT. Nonetheless, this association was not statistically significant and this variant had no protective effect for T2DM. A significant difference was not found in genotypes (CC, CT, and TT) and alleles (C and T) frequency of KCNQ1 rs2237892 SNP between T2DM and control groups (P = 0.475 and P = 0.470, respectively).

Conclusions

Our investigations did not show enough evidence for the presence of an association between KCNQ1 gene rs2237892 polymorphism and risk of T2DM among a group of Iranian patients.
Literature
1.
go back to reference Pal A, McCarthy MI. The genetics of type 2 diabetes and its clinical relevance. Clin Genet. 2013;83(4):297–306.CrossRef Pal A, McCarthy MI. The genetics of type 2 diabetes and its clinical relevance. Clin Genet. 2013;83(4):297–306.CrossRef
2.
go back to reference Stancakova A, Laakso M. Genetics of type 2 diabetes. Endocr Dev. 2016;31:203–20.CrossRef Stancakova A, Laakso M. Genetics of type 2 diabetes. Endocr Dev. 2016;31:203–20.CrossRef
3.
go back to reference International Diabetes Federation. IDF Diabetes Atlas. 6th ed. Brussels: International Diabetes Federation; 2013. International Diabetes Federation. IDF Diabetes Atlas. 6th ed. Brussels: International Diabetes Federation; 2013.
4.
go back to reference Wu Y, Ding Y, Tanaka Y, Zhang W. Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention. Int J Med Sci. 2014;11(11):1185.CrossRef Wu Y, Ding Y, Tanaka Y, Zhang W. Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention. Int J Med Sci. 2014;11(11):1185.CrossRef
5.
go back to reference Prokopenko I, McCarthy MI, Lindgren CM. Type 2 diabetes: new genes, new understanding. Trends Genet. 2008;24(12):613–21.CrossRef Prokopenko I, McCarthy MI, Lindgren CM. Type 2 diabetes: new genes, new understanding. Trends Genet. 2008;24(12):613–21.CrossRef
6.
go back to reference Cui LJ, Chang XY, Zhu LY, Feng G, Zhou T, Zhang CX, et al. Relationship between the polymorphisms in KCNQ1 and type 2 diabetes in Chinese Kazakh population. Genet Mol Res. 2016;15(2). Cui LJ, Chang XY, Zhu LY, Feng G, Zhou T, Zhang CX, et al. Relationship between the polymorphisms in KCNQ1 and type 2 diabetes in Chinese Kazakh population. Genet Mol Res. 2016;15(2).
7.
go back to reference Unoki H, Takahashi A, Kawaguchi T, Hara K, Horikoshi M, Andersen G, et al. SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in east Asian and European populations. Nat Genet. 2008;40(9):1098–102.CrossRef Unoki H, Takahashi A, Kawaguchi T, Hara K, Horikoshi M, Andersen G, et al. SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in east Asian and European populations. Nat Genet. 2008;40(9):1098–102.CrossRef
8.
go back to reference Yasuda K, Miyake K, Horikawa Y, Hara K, Osawa H, Furuta H, et al. Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat Genet. 2008;40(9):1092–7.CrossRef Yasuda K, Miyake K, Horikawa Y, Hara K, Osawa H, Furuta H, et al. Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat Genet. 2008;40(9):1092–7.CrossRef
9.
go back to reference Cho YS, Lee JY, Park KS, Nho CW. Genetics of type 2 diabetes in east Asian populations. Curr Diab Rep. 2012;12(6):686–96.CrossRef Cho YS, Lee JY, Park KS, Nho CW. Genetics of type 2 diabetes in east Asian populations. Curr Diab Rep. 2012;12(6):686–96.CrossRef
10.
go back to reference Li YY, Wang XM, Lu XZ. KCNQ1 rs2237892 C-->T gene polymorphism and type 2 diabetes mellitus in the Asian population: a meta-analysis of 15,736 patients. J Cell Mol Med. 2014;18(2):274–82.CrossRef Li YY, Wang XM, Lu XZ. KCNQ1 rs2237892 C-->T gene polymorphism and type 2 diabetes mellitus in the Asian population: a meta-analysis of 15,736 patients. J Cell Mol Med. 2014;18(2):274–82.CrossRef
11.
go back to reference Barhanin J, Lesage F, Guillemare E, Fink M, Lazdunski M, Romey G. KvLQT1 and IsK (minK) proteins associate to form the IKs cardiac potassium current. Nature. 1996;384(6604):78.CrossRef Barhanin J, Lesage F, Guillemare E, Fink M, Lazdunski M, Romey G. KvLQT1 and IsK (minK) proteins associate to form the IKs cardiac potassium current. Nature. 1996;384(6604):78.CrossRef
12.
go back to reference Saif-Ali R, Muniandy S, Al-Hamodi Z, Lee CS, Ahmed KA, Al-Mekhlafi AM, et al. KCNQ1 variants associate with type 2 diabetes in Malaysian Malay subjects. Ann Acad Med Singap. 2011;40(11):488–92.PubMed Saif-Ali R, Muniandy S, Al-Hamodi Z, Lee CS, Ahmed KA, Al-Mekhlafi AM, et al. KCNQ1 variants associate with type 2 diabetes in Malaysian Malay subjects. Ann Acad Med Singap. 2011;40(11):488–92.PubMed
13.
go back to reference Dai XP, Huang Q, Yin JY, Guo Y, Gong ZC, Lei MX, et al. KCNQ1 gene polymorphisms are associated with the therapeutic efficacy of repaglinide in Chinese type 2 diabetic patients. Clin Exp Pharmacol Physiol. 2012;39(5):462–8.CrossRef Dai XP, Huang Q, Yin JY, Guo Y, Gong ZC, Lei MX, et al. KCNQ1 gene polymorphisms are associated with the therapeutic efficacy of repaglinide in Chinese type 2 diabetic patients. Clin Exp Pharmacol Physiol. 2012;39(5):462–8.CrossRef
14.
go back to reference Tan JT, Nurbaya S, Gardner D, Sandra Y, Tai ES, Ng DP. Genetic variation in KCNQ1 associates with fasting glucose and beta-cell function: a study of 3734 subjects comprising three ethnicities living in Singapore. Diabetes. 2009. Tan JT, Nurbaya S, Gardner D, Sandra Y, Tai ES, Ng DP. Genetic variation in KCNQ1 associates with fasting glucose and beta-cell function: a study of 3734 subjects comprising three ethnicities living in Singapore. Diabetes. 2009.
15.
go back to reference Hu C, Wang C, Zhang R, Ma X, Wang J, Lu J, et al. Variations in KCNQ1 are associated with type 2 diabetes and beta cell function in a Chinese population. Diabetologia. 2009;52(7):1322–5.CrossRef Hu C, Wang C, Zhang R, Ma X, Wang J, Lu J, et al. Variations in KCNQ1 are associated with type 2 diabetes and beta cell function in a Chinese population. Diabetologia. 2009;52(7):1322–5.CrossRef
16.
go back to reference American Diabetes Association (ADA). Standards of medical care in diabetes. Diabetes Care. 2017;40(Suppl 1):S1–S135. American Diabetes Association (ADA). Standards of medical care in diabetes. Diabetes Care. 2017;40(Suppl 1):S1–S135.
17.
go back to reference Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.CrossRef Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.CrossRef
18.
go back to reference Tsai F-J, Yang C-F, Chen C-C, Chuang L-M, Lu C-H, Chang C-T, et al. A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese. PLoS Genet. 2010;6(2):e1000847.CrossRef Tsai F-J, Yang C-F, Chen C-C, Chuang L-M, Lu C-H, Chang C-T, et al. A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese. PLoS Genet. 2010;6(2):e1000847.CrossRef
19.
go back to reference Chen Z, Zhang X, Ma G, Qian Q, Yao Y. Association study of four variants in KCNQ1 with type 2 diabetes mellitus and premature coronary artery disease in a Chinese population. Mol Biol Rep. 2010;37(1):207–12.CrossRef Chen Z, Zhang X, Ma G, Qian Q, Yao Y. Association study of four variants in KCNQ1 with type 2 diabetes mellitus and premature coronary artery disease in a Chinese population. Mol Biol Rep. 2010;37(1):207–12.CrossRef
20.
go back to reference Turki A, Mtiraoui N, Al-Busaidi AS, Khirallah M, Mahjoub T, Almawi WY. Lack of association between genetic polymorphisms within KCNQ1 locus and type 2 diabetes in Tunisian Arabs. Diabetes Res Clin Pract. 2012;98(3):452–8.CrossRef Turki A, Mtiraoui N, Al-Busaidi AS, Khirallah M, Mahjoub T, Almawi WY. Lack of association between genetic polymorphisms within KCNQ1 locus and type 2 diabetes in Tunisian Arabs. Diabetes Res Clin Pract. 2012;98(3):452–8.CrossRef
21.
go back to reference Qi Q, Li H, Loos RJ, Liu C, Wu Y, Hu FB, et al. Common variants in KCNQ1 are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population. Hum Mol Genet. 2009;18(18):3508–15.CrossRef Qi Q, Li H, Loos RJ, Liu C, Wu Y, Hu FB, et al. Common variants in KCNQ1 are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population. Hum Mol Genet. 2009;18(18):3508–15.CrossRef
22.
go back to reference Lee Y-H, Kang ES, Kim SH, Han SJ, Kim CH, Kim HJ, et al. Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population. J Hum Genet. 2008;53(11–12):991.CrossRef Lee Y-H, Kang ES, Kim SH, Han SJ, Kim CH, Kim HJ, et al. Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population. J Hum Genet. 2008;53(11–12):991.CrossRef
23.
go back to reference Zhang W, Wang H, Guan X, Niu Q, Li W. Variant rs2237892 of KCNQ1 is potentially associated with hypertension and macrovascular complications in type 2 diabetes mellitus in a Chinese Han population. Genomics Proteomics Bioinformatics. 2015;13(6):364–70.CrossRef Zhang W, Wang H, Guan X, Niu Q, Li W. Variant rs2237892 of KCNQ1 is potentially associated with hypertension and macrovascular complications in type 2 diabetes mellitus in a Chinese Han population. Genomics Proteomics Bioinformatics. 2015;13(6):364–70.CrossRef
24.
go back to reference Been LF, Ralhan S, Wander GS, Mehra NK, Singh J, Mulvihill JJ, et al. Variants in KCNQ1 increase type II diabetes susceptibility in south Asians: a study of 3,310 subjects from India and the US. BMC Med Genet. 2011;12:18.CrossRef Been LF, Ralhan S, Wander GS, Mehra NK, Singh J, Mulvihill JJ, et al. Variants in KCNQ1 increase type II diabetes susceptibility in south Asians: a study of 3,310 subjects from India and the US. BMC Med Genet. 2011;12:18.CrossRef
25.
go back to reference Tam V, Patel N, Turcotte M, Bossé Y, Paré G, Meyre D. Benefits and limitations of genome-wide association studies. Nat Rev Genet. 2019;1. Tam V, Patel N, Turcotte M, Bossé Y, Paré G, Meyre D. Benefits and limitations of genome-wide association studies. Nat Rev Genet. 2019;1.
26.
go back to reference Poorolajal J. Resistance economy and new population policy in Iran. J Res Health Sci. 2017;17(1):e00367.PubMed Poorolajal J. Resistance economy and new population policy in Iran. J Res Health Sci. 2017;17(1):e00367.PubMed
Metadata
Title
KCNQ1 common genetic variant and type 2 diabetes mellitus risk
Authors
Taraneh Erfani
Negar Sarhangi
Mahdi Afshari
Davood Abbasi
Hamid Reza Aghaei Meybodi
Mandana Hasanzad
Publication date
01-06-2020
Publisher
Springer International Publishing
Published in
Journal of Diabetes & Metabolic Disorders / Issue 1/2020
Electronic ISSN: 2251-6581
DOI
https://doi.org/10.1007/s40200-019-00473-4

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