The association of T2D with a set of 121 genetic variants

Type 2 Diabetes Mellitus (T2D) is classified as a multifactorial and polygenic disease. The search for T2D associated DNA variants is complex; population studies are essential to assess the genetic influence. Association of T2D with a set of 121 genetic variants (63 located in 37 genes and four intergenic regions, and 58 informative ancestry markers) was assessed in 442 subjects (262 cases and 180 controls) from Northeastern Mexico. The approach was made using different transmission models: dominant, recessive, and MLMM. Age, body mass index (BMI), and gender data were obtained and considered as cofactors (gene-environment (G × E) interaction) in a multi-locus genetic model, and the ORs were calculated. Genetic variants were classified as Regulatory Region Variants, Nonsense-mediated decay transcript variants, and Missense Variants. Thirteen genetic variants showed association (P&lt;0.05 after Bonferroni correction), being the most significant variants <i>RPTOR</i> (rs12950541 p&lt; 2.18x10^-32) and <i>UCP3 </i>(rs7930460 and rs1800849 p&lt;8.67x 10^-16 and 4.64x 10^-7, respectively) with the additive genetic model (MLMM). These results can contribute to understanding the role of genetic variants on the risk of developing T2D in the Northeastern Mexican mestizo population and support future studies to evaluate and validate as biomarkers to improve genetic assessment via precision medicine.

2型糖尿病（Type 2 Diabetes Mellitus, T2D）是一种多因素性多基因疾病。探寻与T2D相关的DNA变异体颇具挑战性；群体研究对于评估其遗传影响至关重要。本研究针对墨西哥东北部的442名受试者（262例病例、180例对照），分析了121个遗传变异体与T2D的关联情况：其中63个变异体分布于37个基因内、4个位于基因间区，另有58个为祖先信息标记。本次分析采用了三种不同的传递模型：显性模型、隐性模型以及多基因座混合线性模型（MLMM）。研究人员收集了受试者的年龄、体重指数（BMI）与性别数据，并将其作为协变量（基因-环境（G×E）交互作用）纳入多基因座遗传模型，同时计算了比值比（OR）。本研究中的遗传变异体可分为三类：调控区变异体、无义介导的降解转录本变异体以及错义变异体。共有13个遗传变异体呈现出显著关联（Bonferroni校正后P<0.05），其中基于加性遗传模型（MLMM）分析得到的最具统计学显著性的变异体为<i>RPTOR</i>基因的rs12950541（P<2.18×10^-32），以及<i>UCP3</i>基因的rs7930460（P<8.67×10^-16）与rs1800849（P<4.64×10^-7）。本研究结果有助于阐明遗传变异体在墨西哥东北部混血人群T2D发病风险中的作用，并可为未来将上述变异体作为生物标志物、通过精准医学优化遗传评估的相关研究提供理论支撑。