Wang Yinghong, Wang Yongtao, Adi Dilare, He XiaoDong, Liu Fen, Abudesimu Asiya, Fu Zhenyan, Ma Yitong
Department of Cardiology.
Center of Health Management, the First Affiliated Hospital of Xinjiang Medical University.
Medicine (Baltimore). 2020 Jul 2;99(27):e20924. doi: 10.1097/MD.0000000000020924.
Disabled-2 (Dab2) is a clathrin and cargo-binding endocytic adaptor protein that plays a role in cellular trafficking of low-density lipoprotein receptor (LDLR). However, little is known about its involvement in coronary artery disease (CAD). Here, we aimed to investigate the association between Dab2 single-nucleotide polymorphisms (SNPs) and CAD in Chinese Han and Uyghur populations.We performed a case-control study in CAD group that consisted of 621 Han and 346 Uygurs, and the age and gender matched control group consisted of 611 Han and 405 Uygurs. The clinicopathological characteristics of these subjects were analyzed. Genotyping of 4 SNPs (rs1050903, rs2855512, rs11959928, and rs2255280) of the Dab2 gene was performed in all subjects with an improved multiplex ligase detection reaction method.The distribution of the genotype, dominant model (AA vs. AC + CC), as well as allele frequencies of both rs2855512 and rs2255280, was significantly different between CAD patients and control subjects in Han population but not in Uyghur population. AA genotype may be a risk factor for CAD. For Han population, statistical significant correlation between dominant model for both SNPs (AA) and CAD was found after multivariate adjustment. After multivariate adjustment in the Han population, we speculate that rs285512 A allele and rs2255280 A allele may be potentially associated with the onset of coronary heart disease. Individuals with the AA genotype had an OR of 1.44 (95% CI: 1.10-1.88, P = .01, rs2855512) and 1.41 (95% CI: 1.08-1.85, P = .01, rs2255280) for CAD compared with individuals with the AC or CC genotype, respectively.Our data indicates that the AA genotype of rs2855512 and rs2255280 in the Dab2 gene may be a genetic marker of CAD risk in Chinese Han population.
Disabled-2（Dab2）是一种网格蛋白和货物结合内吞衔接蛋白，在低密度脂蛋白受体（LDLR）的细胞运输中发挥作用。然而，其与冠状动脉疾病（CAD）的关系尚不清楚。在此，我们旨在研究中国汉族和维吾尔族人群中Dab2单核苷酸多态性（SNP）与CAD之间的关联。我们对由621名汉族和346名维吾尔族组成的CAD组以及年龄和性别匹配的由611名汉族和405名维吾尔族组成的对照组进行了病例对照研究。分析了这些受试者的临床病理特征。采用改进的多重连接酶检测反应方法对所有受试者的Dab2基因的4个SNP（rs1050903、rs2855512、rs11959928和rs2255280）进行基因分型。汉族CAD患者与对照组之间，rs2855512和rs2255280的基因型分布、显性模型（AA与AC+CC）以及等位基因频率存在显著差异，而维吾尔族人群中无显著差异。AA基因型可能是CAD的一个危险因素。对于汉族人群，多因素调整后发现两个SNP（AA）的显性模型与CAD之间存在统计学显著相关性。在汉族人群多因素调整后，我们推测rs285512 A等位基因和rs2255280 A等位基因可能与冠心病的发病存在潜在关联。与AC或CC基因型个体相比，AA基因型个体患CAD的比值比分别为1.44（95%CI：1.10 - 1.88，P = 0.01，rs2855512）和1.41（95%CI：1.08 - 1.85，P = 0.01，rs2255280）。我们的数据表明，Dab2基因中rs2855512和rs2255280的AA基因型可能是中国汉族人群CAD风险的遗传标志物。
