College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Esipe Créteil, Ingénierie Spécialisée en Biomédical et Santé, Université Paris-Est Créteil, Créteil, France.
Am J Hum Biol. 2021 Jan;33(1):e23434. doi: 10.1002/ajhb.23434. Epub 2020 May 23.
Type 2 diabetes mellitus (T2DM) has a multifactorial etiology involving a complex interplay between genes and the environment. The prevalence of T2DM among the countries of the Gulf Corporation Council (GCC), including the United Arab Emirates (UAE), ranks among the top 15 in the world. A number of studies have shown an increase in T2DM risk for the "TT" genotype at the rs4506565 and rs12255372 Single Nucleotide Polymorphisms (SNP) of the TCF7L2 gene. However, the association between TCF7L2 and T2DM still needs to be investigated in the UAE population. Therefore, this study analyzed the potential associations with rs4506565 and rs12255372 in UAE subjects.
For this case-control study, T2DM patients (n = 890) and healthy subjects (n = 686) were genotyped using a Taqman Real-Time PCR assay. Statistical analysis was performed with the resulting data using the R (version 3.3.1) and STATA (version 13) software packages.
The rs12255372 SNP was significantly associated with T2DM (OR = 1.16, 95% CI = 1.00-1.34; P = .042). However, no significant association was found for the rs4506565 SNP (P = .120). After gender stratification, a significant association was found for both SNPs in males (P = .009 and P = .021). Interestingly, we found the interaction between the SNP rs4506565 with gender alone (P = .032) and in conjunction with BMI and age (P = .036) confers associations with T2DM.
These findings suggest that the genetic variants of the TCF7L2 gene are associated with an increased susceptibility to T2DM, especially in Emirati males. Our study also highlights the impact of biological and environmental risk factors including age, BMI, and gender on the genetic susceptibility to T2DM.
2 型糖尿病(T2DM)具有多因素病因,涉及基因与环境之间的复杂相互作用。在海湾合作委员会(GCC)国家中,包括阿拉伯联合酋长国(阿联酋),T2DM 的患病率位居世界前 15 位。许多研究表明,TCF7L2 基因的 rs4506565 和 rs12255372 单核苷酸多态性(SNP)中的“TT”基因型会增加 T2DM 的风险。然而,在阿联酋人群中,TCF7L2 与 T2DM 之间的关联仍需要进一步研究。因此,本研究分析了阿联酋人群中 rs4506565 和 rs12255372 与 T2DM 之间的潜在关联。
在这项病例对照研究中,使用 Taqman 实时 PCR 检测法对 890 名 T2DM 患者和 686 名健康受试者进行了基因分型。使用 R(版本 3.3.1)和 STATA(版本 13)软件包对所得数据进行了统计分析。
rs12255372 SNP 与 T2DM 显著相关(OR=1.16,95%CI=1.00-1.34;P=0.042)。然而,rs4506565 SNP 与 T2DM 无显著相关性(P=0.120)。在性别分层后,两个 SNP 在男性中均与 T2DM 显著相关(P=0.009 和 P=0.021)。有趣的是,我们发现 SNP rs4506565 仅与性别(P=0.032)以及与 BMI 和年龄(P=0.036)的相互作用与 T2DM 相关。
这些发现表明,TCF7L2 基因的遗传变异与 T2DM 的易感性增加有关,尤其是在阿联酋男性中。我们的研究还强调了年龄、BMI 和性别等生物和环境风险因素对 T2DM 遗传易感性的影响。