研究表明维生素D能够促进胰岛素分泌、改善胰岛素抵抗，在糖尿病的发病及血糖控制中发挥着重要作用。维生素D受体基因（VDR）、结合蛋白基因（Gc）以及细胞色素P450基因（CYP2R1）是维生素D代谢通路上的关键基因，这些基因变异将影响维生素D功能的发挥并最终导致2型糖尿病（T2DM）患病风险增加。课题组前期研究发现VDR、Gc基因的SNP多态性与T2DM的发病密切相关，鉴于基因组拷贝数变异和DNA甲基化在疾病的发展中也扮演重要的角色，本研究拟建立T2DM病例对照家系资源库，采用荧光定量PCR及高效液相色谱等技术对受试者VDR、Gc和CYP2R1基因拷贝数变异及其DNA甲基化水平进行分析测定，结合受试者的生活环境，运用多因子降维、logistic回归等统计学手段和方法综合评价环境、遗传易感性及表观遗传学修饰等在T2DM中的作用机理，以及三者之间的交互作用，为T2DM的综合防治提供科学依据。

Many studies have supposed that vitamin D play an important role in the process of type 2 diabetes mellitus because it can promote the secretion of insulin and improve in sulinresistance. VDR, Gc and CYP2R1 are the key genes on the metabolic pathways of Vitamin D. The abnormal variants in these genes will deteriorate the function of vitamin D in vivo and increase the risk of diabetes mellitus. Therefore, based on the previous studies this project will use the case-control family study and laboratory research methods to make clear the association between the copy number variants and DNA methylation in VDR, Gc and CYP2R1 genes and the susceptibility of type 2 diabetes mellitus. The real-time fluorescent quantitative PCR and HPLC will be used to detect the copy number variants and DNA methylation in VDR, Gc and CYP2R1 genes of the subjects. Then combined the living environment, we will use a variety of statistical methods and software to comprehensively assess the causes and the roles of the environment, genetic heritage and epigenetic modification and their interaction in the process of type 2 diabetes mellitus, which will provide a scientific basis for comprehensive control of this chronic disease.