Fatima Syeda Sadia, Chaudhry Bushra, Khan Taseer Ahmed, Farooq Saad
Syeda Sadia Fatima, MBBS, MPhil, PhD, Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistani.
Bushra Chaudhry, PhD, Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistani.
Pak J Med Sci. 2016 Nov-Dec;32(6):1380-1385. doi: 10.12669/pjms.326.11052.
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.
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.
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.
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.
关于妊娠期糖尿病（GDM）的遗传学研究相对较少；此外，巴基斯坦孕妇中KCNQ1基因多态性的数据有限。我们旨在确定KCNQ1 rs2237895在GDM患者和正常孕妇对照组中的频率及其与GDM相关表型的关联。
本研究根据国际糖尿病与妊娠研究协会的标准，对637名孕中期女性（429名对照者和208例患者）进行了分类。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法和测序技术对她们的血样进行KCNQ1单核苷酸多态性（SNP）rs2237895基因分型。进行空腹及葡萄糖负荷后两小时的血糖水平、血清糖化血红蛋白（HbA1c）、胰岛素检测以及人体测量评估。采用Pearson卡方检验、Mann-Whitney U检验和回归分析。p值<0.05被认为具有统计学意义。
所检测的变异基因型处于Hardy-Weinberg平衡状态（p>0.05）。rs2237895与GDM相关（比值比[OR] 2.281；1.388 - 3.746：p <0.001），在对年龄和体重指数进行多次校正后仍具有统计学意义（OR 2.068；1.430 - 2.997：p = 0.005）。C等位基因与研究对象的胰岛素水平和稳态模型评估的胰岛素抵抗（HOMA-IR）呈正相关。
本研究表明，KCNQ1 rs2237895多态性可能与巴基斯坦人群患GDM的风险相关，并且与较高的血糖水平和胰岛素抵抗有关。需要进一步开展大规模研究以巩固该多态性的功能方面的研究。
