Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical College, The Affiliated XuZhou Hospital of Medical College of Southeast University, Jiangsu 221009, China; Xuzhou Institute of Medical Sciences, Xuzhou Institute of Diabetes, Xuzhou, Jiangsu 221000, China.
Department of Vascular and Thyroid Surgeon, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical College, The Affiliated XuZhou Hospital of Medical College of Southeast University, Jiangsu 221009, China.
J Diabetes Complications. 2021 Apr;35(4):107855. doi: 10.1016/j.jdiacomp.2021.107855. Epub 2021 Jan 29.
The understanding of the genetic basis of type 2 diabetes mellitus (T2DM) has progressed rapidly, but the interactions among common genetic variants and metabolic risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and metabolic environments on the risk of T2DM. Obesity is emerging as an independent risk factor for T2DM and arterial stiffness. Here, we examined the effect of the rs9356744 polymorphism in the body mass index (BMI) gene CDKAL1 on the risk of T2DM in East Asians and particularly assessed the interactions between this polymorphism and other metabolic risk factors. A total of 1975 subjects in whom the rs9356744 polymorphism had been detected in the CDKAL1 gene were enrolled in this study. The height, weight, blood pressure and relevant markers, including glucose, lipids, liver and renal function, of the participants were successfully measured. Pulse wave velocity (PWV) was measured using an automatic wave form analyzer. At baseline, we found a significant association between BMI and rs9356744 genotypes (CC, CT, TT) (P = 0.048). After adjusting for confounding factors, including sex, age and BMI, participants carrying the T allele of rs9356744 showed a lower incidence of T2DM. Further adjustment for blood pressure and lipids did not appreciably change the results (P = 0.019, 0.009, 0.015, respectively). We found significant interactions between the rs9356744 polymorphism and high-density lipoprotein (HDL), serum uric acid (SUA) and carotid-femoral pulse wave velocity (cf-PWV) in relation to T2DM incidence (P for interaction = 0.007, 0.002, 0.004, respectively), especially in the group with the lowest SUA level and the group with the highest HDL and cf-PWV levels (P for trend = 0.006, 0.008, 0.018, respectively). Furthermore, we found a significant interaction between the rs9356744 polymorphism and cf-PWV in relation to the level of 2-h plasma glucose in the oral glucose tolerance test (OGTT) (P for interaction = 0.0341). In summary, the T allele of rs9356744 was an independent protective factor for T2DM. There were significant interactions between rs9356744 and HDL, SUA, and cf-PWV in relation to T2DM risk.
2 型糖尿病（T2DM）的遗传基础研究进展迅速，但在具有足够统计效力的研究中，尚未系统研究常见遗传变异与代谢危险因素之间的相互作用。因此，我们旨在量化遗传和代谢环境对 T2DM 风险的综合影响。肥胖症正成为 T2DM 和动脉僵硬度的独立危险因素。在这里，我们研究了 BMI 基因 CDKAL1 中的 rs9356744 多态性对东亚人 T2DM 风险的影响，并特别评估了该多态性与其他代谢危险因素之间的相互作用。本研究共纳入了 1975 名检测到 CDKAL1 基因中 rs9356744 多态性的受试者。成功测量了参与者的身高、体重、血压和相关标志物，包括血糖、血脂、肝肾功能。使用自动波形成分析仪测量脉搏波速度（PWV）。在基线时，我们发现 BMI 与 rs9356744 基因型（CC、CT、TT）之间存在显著关联（P=0.048）。在调整包括性别、年龄和 BMI 在内的混杂因素后，携带 rs9356744T 等位基因的参与者 T2DM 的发生率较低。进一步调整血压和血脂并未明显改变结果（P=0.019、0.009、0.015，分别）。我们发现 rs9356744 多态性与高密度脂蛋白（HDL）、血清尿酸（SUA）和颈动脉-股动脉脉搏波速度（cf-PWV）之间存在显著的相互作用，与 T2DM 发生率有关（P 交互=0.007、0.002、0.004，分别），尤其是在 SUA 水平最低的组和 HDL 和 cf-PWV 水平最高的组（P 趋势=0.006、0.008、0.018，分别）。此外，我们发现 rs9356744 多态性与 cf-PWV 之间存在与口服葡萄糖耐量试验（OGTT）中 2 小时血浆葡萄糖水平相关的显著相互作用（P 交互=0.0341）。总之，rs9356744 的 T 等位基因是 T2DM 的独立保护因素。rs9356744 与 HDL、SUA 和 cf-PWV 之间存在与 T2DM 风险相关的显著相互作用。
