KCNQ1 Rs2237895 Polymorphism is Associated with Gestational Diabetes in Pakistani Women

Overview

Journal Pak J Med Sci

Specialty General Medicine

Date 2017 Jan 14

PMID 28083030

Citations 12

Authors

Syeda Sadia Fatima

Bushra Chaudhry

Taseer Ahmed Khan

Saad Farooq

Affiliations

Soon will be listed here.

Abstract

Background And Objective: Genetic studies on gestational diabetes (GDM) are relatively scarce; moreover, limited data is available for KCNQ1 polymorphism in Pakistani pregnant women. We aimed to determine the frequency of KCNQ1 rs2237895 in GDM and normal pregnant controls and its association with GDM-related phenotypes.

Methods: A total of 637 pregnant females (429 controls and 208 cases) in their second trimester were classified according to the International Association of the Diabetes and Pregnancy Study criteria in this study. Their blood samples were genotyped for KCNQ1 SNP rs2237895 using PCR-RFLP method and sequencing. Fasting and two hour-post glucose load blood levels, serum HbA1c, insulin, and anthropometric assessment was performed.: Pearson's Chi Square test, Mann- Whitney U test, and regression analyses were performed. A p-value of <0.05 was considered significant.

Results: The variant genotyped was in Hardy-Weinberg equilibrium (p>0.05). The rs2237895 showed an association with GDM (OR 2.281; 1.388-3.746: p <0.001) and remained significant after multiple adjustments for age and body mass index (OR 2.068; 1.430-2.997: p=0.005). The C allele showed positive association with insulin level, and HOMA-IR in study subjects.

Conclusions: This study identifies that KCNQ1 rs2237895 polymorphisms might be associated with risk of GDM in Pakistani population and that it is related to higher glucose levels and insulin resistance. Further large scale studies are required to consolidate on the functional aspect of this polymorphism.

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References

Zhou Q, Zhang K, Li W, Liu J, Hong J, Qin S . Association of KCNQ1 gene polymorphism with gestational diabetes mellitus in a Chinese population. Diabetologia. 2009; 52(11):2466-2468. DOI: 10.1007/s00125-009-1500-y. View

Moss A, Shimizu W, Wilde A, Towbin J, Zareba W, Robinson J . Clinical aspects of type-1 long-QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene. Circulation. 2007; 115(19):2481-9. PMC: 3332528. DOI: 10.1161/CIRCULATIONAHA.106.665406. View

Kwak S, Kim T, Cho Y, Choi S, Jang H, Park K . Polymorphisms in KCNQ1 are associated with gestational diabetes in a Korean population. Horm Res Paediatr. 2010; 74(5):333-8. DOI: 10.1159/000313918. View

Shin H, Park B, Shin H, Kim J, Park S, Kim B . Association of KCNQ1 polymorphisms with the gestational diabetes mellitus in Korean women. J Clin Endocrinol Metab. 2009; 95(1):445-9. DOI: 10.1210/jc.2009-1393. View

Chon S, Kim S, Cho N, Min D, Hwang Y, Mamura M . Association of variants in PPARγ², IGF2BP2, and KCNQ1 with a susceptibility to gestational diabetes mellitus in a Korean population. Yonsei Med J. 2013; 54(2):352-7. PMC: 3575978. DOI: 10.3349/ymj.2013.54.2.352. View

Yasuda K, Miyake K, Horikawa Y, Hara K, Osawa H, Furuta H . Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat Genet. 2008; 40(9):1092-7. DOI: 10.1038/ng.207. View

Grallert H, Herder C, Marzi C, Meisinger C, Wichmann H, Rathmann W . Association of genetic variation in KCNQ1 with type 2 diabetes in the KORA surveys. Horm Metab Res. 2009; 42(2):149-51. DOI: 10.1055/s-0029-1241170. View

Khan K, Rizvi J, Qureshi R, Mazhar R . Gestational diabetes in a developing country, experience of screening at the Aga Khan University Medical Centre, Karachi. J Pak Med Assoc. 1991; 41(2):31-3. View

Zia A, Wang X, Bhatti A, Demirci F, Zhao W, Rasheed A . A replication study of 49 Type 2 diabetes risk variants in a Punjabi Pakistani population. Diabet Med. 2015; 33(8):1112-7. DOI: 10.1111/dme.13012. View

10.

Ferrara A . Increasing prevalence of gestational diabetes mellitus: a public health perspective. Diabetes Care. 2007; 30 Suppl 2:S141-6. DOI: 10.2337/dc07-s206. View

11.

Jawa A, Raza F, Qamar K, Jawad A, Akram J . Gestational diabetes mellitus is rare in primigravida Pakistani women. Indian J Endocrinol Metab. 2011; 15(3):191-3. PMC: 3156539. DOI: 10.4103/2230-8210.83404. View

12.

Rees S, Hydrie M, Shera A, Kumar S, OHare J, Barnett A . Replication of 13 genome-wide association (GWA)-validated risk variants for type 2 diabetes in Pakistani populations. Diabetologia. 2011; 54(6):1368-74. DOI: 10.1007/s00125-011-2063-2. View

13.

Ao D, Wang H, Wang L, Song J, Yang H, Wang Y . The rs2237892 Polymorphism in KCNQ1 Influences Gestational Diabetes Mellitus and Glucose Levels: A Case-Control Study and Meta-Analysis. PLoS One. 2015; 10(6):e0128901. PMC: 4454508. DOI: 10.1371/journal.pone.0128901. View

14.

Unoki H, Takahashi A, Kawaguchi T, Hara K, Horikoshi M, Andersen G . SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nat Genet. 2008; 40(9):1098-102. DOI: 10.1038/ng.208. View

15.

Liu Y, Zhou D, Zhang D, Chen Z, Zhao T, Zhang Z . Variants in KCNQ1 are associated with susceptibility to type 2 diabetes in the population of mainland China. Diabetologia. 2009; 52(7):1315-21. PMC: 2688614. DOI: 10.1007/s00125-009-1375-y. View

16.

MacDonald P, Ha X, Wang J, Smukler S, Sun A, Gaisano H . Members of the Kv1 and Kv2 voltage-dependent K(+) channel families regulate insulin secretion. Mol Endocrinol. 2001; 15(8):1423-35. DOI: 10.1210/mend.15.8.0685. View

17.

Cho Y, Kim T, Lim S, Choi S, Shin H, Lee H . Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population. Diabetologia. 2008; 52(2):253-61. DOI: 10.1007/s00125-008-1196-4. View

18.

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. 2009; 37(1):207-12. DOI: 10.1007/s11033-009-9597-0. View

19.

Iqbal R, Rafique G, Badruddin S, Qureshi R, Cue R, Gray-Donald K . Increased body fat percentage and physical inactivity are independent predictors of gestational diabetes mellitus in South Asian women. Eur J Clin Nutr. 2006; 61(6):736-42. DOI: 10.1038/sj.ejcn.1602574. View

20.

Holmkvist J, Banasik K, Andersen G, Unoki H, Jensen T, Pisinger C . The type 2 diabetes associated minor allele of rs2237895 KCNQ1 associates with reduced insulin release following an oral glucose load. PLoS One. 2009; 4(6):e5872. PMC: 2689931. DOI: 10.1371/journal.pone.0005872. View