School of Public Health, Wuhan University of Science and Technology, Wuhan, China.
Department of Clinical, Bijie Medical College, Bijie, China.
Front Endocrinol (Lausanne). 2022 Jul 29;13:916590. doi: 10.3389/fendo.2022.916590. eCollection 2022.
To investigate the correlation between transcription factor 7-like 2 (TCF7L2) gene polymorphisms and gestational diabetes mellitus (GDM) risk in the central Chinese population.
This case-control study examined the association of seven gene single-nucleotide polymorphisms (SNPs) (rs11196218, rs4506565, rs7895340, rs7901695, rs11196205, rs12243326, and rs290487) with GDM risk in the central Chinese population (843 GDM and 877 controls). The clinical information and blood samples were collected by trained interviewers and nurses. Genotyping of SNPs was conducted on the Sequenom MassARRAY platform. Statistical analyses including -test, ANOVA, chi-square test, Fisher's exact test, and logistic regression were performed.
Differences in age, pre-pregnant body mass index (BMI), and family history of type 2 diabetes mellitus (T2DM) between the case and control groups were significant ( < 0.05). Compared with the wild-type genotype, pregnant women with genotypes of rs4506565-AT ( = 1.89, 95%: 1.18-3.02), rs7895340 GA ( = 1.93, 95%: 1.06-3.54), rs7901695-TC ( = 1.79, 95%: 1.11-2.88), and rs11196205-GC ( = 2.15, 95%: 1.16-3.98) had a significantly higher risk of GDM, adjusted by age, pre-pregnant BMI, and family history of T2DM. Functional annotation showed that all these four SNPs fell in the functional elements of human pancreatic islets. Further cumulative effects analysis concluded that when participants carried all these four risk genotypes, the risk of GDM was 3.51 times ( = 3.51, 95%: 1.38-8.90) than that of those without any risk genotypes.
The findings of this study suggested that rs4506565, rs7895340, rs7901695, and rs11196205 were the genetic susceptibility SNPs of GDM in the central Chinese population. Further studies are needed to validate our findings and clarify the underlying mechanisms.
探讨转录因子 7 样 2(TCF7L2)基因多态性与中国中部人群妊娠期糖尿病(GDM)发病风险的相关性。
采用病例对照研究,分析中国中部人群(843 例 GDM 患者和 877 例对照)中 7 个基因单核苷酸多态性(SNP)(rs11196218、rs4506565、rs7895340、rs7901695、rs11196205、rs12243326 和 rs290487)与 GDM 发病风险的关系。由经过培训的调查员和护士采集临床资料和血样。采用Sequenom MassARRAY 平台进行 SNP 基因分型。采用 -检验、方差分析、卡方检验、Fisher 确切概率法和 logistic 回归进行统计学分析。
病例组与对照组在年龄、孕前体质量指数(BMI)和 2 型糖尿病家族史方面存在差异( < 0.05)。与野生型基因型相比,rs4506565-AT(比值比[OR] = 1.89,95%置信区间[CI]:1.18-3.02)、rs7895340-GA(OR = 1.93,95%CI:1.06-3.54)、rs7901695-TC(OR = 1.79,95%CI:1.11-2.88)和 rs11196205-GC(OR = 2.15,95%CI:1.16-3.98)基因型的孕妇 GDM 发病风险显著升高,校正年龄、孕前 BMI 和 2 型糖尿病家族史后差异有统计学意义。功能注释显示,这 4 个 SNP 均位于人胰岛的功能元件中。进一步的累积效应分析表明,当参与者携带所有这 4 个风险基因型时,GDM 的发病风险是无任何风险基因型参与者的 3.51 倍(OR = 3.51,95%CI:1.38-8.90)。
本研究结果提示 rs4506565、rs7895340、rs7901695 和 rs11196205 是中国中部人群 GDM 的遗传易感 SNP,还需要进一步的研究来验证我们的发现并阐明其潜在机制。