Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China.
J Diabetes Complications. 2021 Mar;35(3):107829. doi: 10.1016/j.jdiacomp.2020.107829. Epub 2020 Dec 31.
To assess the associations of single-nucleotide polymorphisms (SNPs) and methylation of transcription factor 7-like 2 (TCF7L2) gene with type 2 diabetes mellitus (T2DM) risk and further explore the interactions among SNPs, methylation, and environmental factors involved in T2DM risk.
We conducted a nested case-control study with 290 pairs of T2DM cases and matched controls. We genotyped 3 SNPs of TCF7L2 in all included participants and tested 14 CpG loci of TCF7L2 in 76 pairs of cases and controls. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for T2DM risk according to SNPs and methylation of TCF7L2. Multifactor dimensionality reduction (MDR) analysis was used to explore the potential TCF7L2 gene-environment interactions in T2DM risk.
We found no statistically significant association between the TCF7L2 polymorphisms and T2DM risk. We observed significant positive associations of methylation at CpG5 and CpG7_8 with T2DM risk. For each 1% increase in DNA methylation at CpG5 and CpG7_8, T2DM risk increased 12% (OR 1.12, 95% CI 1.01-1.25) and 32% (OR 1.32, 95% CI 1.07-1.63), respectively. Additionally, MDR analyses identified significant SNP-environment interactions among rs290487, alcohol drinking, and hypertension and methylation-environment interactions among CpG5, CpG7_8 and hypertension (P <0.05).
TCF7L2 polymorphisms were not independently associated with T2DM risk. However, TCF7L2 methylation were positively associated with T2DM risk in rural Chinese adults. Interactions among TCF7L2 polymorphisms, TCF7L2 methylation and environmental factors also suggest a possible etiologic pattern for T2DM.
评估单核苷酸多态性（SNP）和转录因子 7 样 2（TCF7L2）基因的甲基化与 2 型糖尿病（T2DM）风险的关联，并进一步探讨 SNP、甲基化与 T2DM 风险相关的环境因素之间的相互作用。
我们进行了一项巢式病例对照研究，共纳入 290 对 T2DM 病例和匹配对照。我们对所有纳入的参与者进行了 TCF7L2 的 3 个 SNP 基因分型，并在 76 对病例和对照中检测了 TCF7L2 的 14 个 CpG 位点。条件 logistic 回归模型用于估计 SNP 和 TCF7L2 甲基化与 T2DM 风险之间的比值比（OR）和 95%置信区间（95%CI）。多因素维度缩减（MDR）分析用于探索 T2DM 风险中 TCF7L2 基因-环境相互作用的潜在模式。
我们未发现 TCF7L2 多态性与 T2DM 风险之间存在统计学显著关联。我们观察到 CpG5 和 CpG7_8 甲基化与 T2DM 风险呈显著正相关。CpG5 和 CpG7_8 的 DNA 甲基化每增加 1%，T2DM 风险分别增加 12%（OR 1.12，95%CI 1.01-1.25）和 32%（OR 1.32，95%CI 1.07-1.63）。此外，MDR 分析发现 rs290487、饮酒和高血压之间的 SNP-环境相互作用以及 CpG5、CpG7_8 和高血压之间的甲基化-环境相互作用具有统计学意义（P<0.05）。
TCF7L2 多态性与 T2DM 风险无独立关联。然而，在中国农村成年人中，TCF7L2 甲基化与 T2DM 风险呈正相关。TCF7L2 多态性、甲基化与环境因素之间的相互作用也提示 T2DM 可能存在一种病因模式。
