KCNQ1 rs2237895 polymorphism is associated with Gestational Diabetes in Pakistani Women

Syeda Sadia Fatima, Bushra Chaudhry, Taseer Ahmed Khan, Saad Farooq, Syeda Sadia Fatima, Bushra Chaudhry, Taseer Ahmed Khan, Saad Farooq

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.

Keywords: Body mass index; GWAS; Gestational Diabetes Mellitus; KCNQ1; SNP.

Conflict of interest statement

Declaration of interest: The authors declare that they have no conflict of interest.

Figures

Fig.1
Fig.1
(A-C): Gel Electrophoresis and Sequencing Chromatogram of KCNQ1 SNPs. Where M is the 50bp DNA marker and B are negative controls in the PCR reaction. A: PCR amplification shown as bands on 2% agarose gel for rs2237895 (218bp) samples numbered 1-4. B: RFLP fragment [3 homozygous mutated: 140bp/78bp (C/C) for samples number 1, 3 & 4; 1 heterozygous carrier: 218bp/140bp/78bp (A/C)] for sample numbered 2 respectively. C: Sequencing Chromatograms showing the mutations as dot and highlighted section in the aligned sequence.

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