1 Madras Diabetes Research Foundation , Chennai, India .
3 SRC Diabetes Care Centre , Erode, India .
Diabetes Technol Ther. 2015 Jul;17(7):462-7. doi: 10.1089/dia.2014.0349. Epub 2015 Feb 27.
This study examined the association in a South Indian population with gestational diabetes mellitus (GDM) of type 2 diabetes risk variants that have previously conferred susceptibility to GDM in other populations.
The study groups comprised 518 women with GDM and 910 pregnant women with normal glucose tolerance (NGT). Women with GDM were recruited from a tertiary diabetes center in Chennai, in south India, and NGT women were selected from antenatal clinics also in Chennai. Genomic DNA was isolated from whole blood using the phenol chloroform method. Twelve previously reported GDM-associated single nucleotide polymorphisms (SNPs) in or near nine loci were genotyped using the MassARRAY™ system (Sequenom, San Diego, CA).
Among the 12 SNPs genotyped, 11 SNPs were in Hardy-Weinberg equilibrium and had a call rate of >95%. Of the 11 SNPs previously associated with GDM in other populations, significant association was observed only with the rs7754840 and rs7756992 SNPs of the CDK5 regulatory subunit associated protein 1-like 1 (CDKAL1) gene in this population. The minor alleles of the SNPs rs7754840 and rs7756992 showed significant susceptibility to GDM with an odds ratio of 1.34 (95% confidence interval, 1.12-1.60; P = 0.0013) and 1.45 (95% confidence interval, 1.21-1.72; P = 0.00004), respectively.
The rs7754840 and rs7756992 SNPs of the CDKAL1 gene were found to be associated with GDM in this south Indian population. This is the first study describing genetic susceptibility of GDM in Asian Indians.
本研究在一个南印度人群中,检测了与妊娠糖尿病(GDM)相关的 2 型糖尿病风险变异体,这些变异体先前在其他人群中与 GDM 易感性相关。
研究组包括 518 名 GDM 妇女和 910 名糖耐量正常(NGT)的孕妇。GDM 妇女来自印度南部钦奈的一个三级糖尿病中心,NGT 妇女则选自钦奈的产前诊所。使用苯酚-氯仿法从全血中分离基因组 DNA。使用 MassARRAY™系统(Sequenom,圣地亚哥,加利福尼亚州)对 9 个基因座内或附近的 12 个先前报道的与 GDM 相关的单核苷酸多态性(SNP)进行基因分型。
在 12 个基因分型的 SNP 中,有 11 个 SNP 处于 Hardy-Weinberg 平衡状态,且具有>95%的呼叫率。在其他人群中与 GDM 相关的 11 个 SNP 中,仅在本人群中观察到与细胞周期蛋白依赖性激酶 5 调节亚单位相关蛋白 1 样 1(CDKAL1)基因的 rs7754840 和 rs7756992 SNP 存在显著相关性。SNP rs7754840 和 rs7756992 的次要等位基因对 GDM 具有显著的易感性,其比值比分别为 1.34(95%置信区间,1.12-1.60;P = 0.0013)和 1.45(95%置信区间,1.21-1.72;P = 0.00004)。
在这个南印度人群中,CDKAL1 基因的 rs7754840 和 rs7756992 SNP 与 GDM 相关。这是第一项描述亚洲印度人 GDM 遗传易感性的研究。