Department of Biomedical Science, College of Life Science, CHA University, Seongnam, 13488, Korea.
Department of Cardiology, CHA Bundang Medical Center, CHA University, Seongnam, 13496, Korea.
Sci Rep. 2020 Oct 1;10(1):16294. doi: 10.1038/s41598-020-73048-6.
The aim of this study was to identify novel genetic markers related to coronary artery disease (CAD) using a whole-exome sequencing (WES) approach and determine any associations between the selected gene polymorphisms and CAD prevalence. CUBN, HNF1A and LIPC gene polymorphisms related to CAD susceptibility were identified using WES screening. Possible associations between the five gene polymorphisms and CAD susceptibility were examined in 452 CAD patients and 421 control subjects. Multivariate logistic regression analyses indicated that the CUBN rs2291521GA and HNF1A rs55783344CT genotypes were associated with CAD (GG vs. GA; adjusted odds ratio [AOR] = 1.530; 95% confidence interval [CI] 1.113-2.103; P = 0.002 and CC vs. CT; AOR = 1.512; 95% CI 1.119-2.045; P = 0.007, respectively). The CUBN rs2291521GA and HNF1A rs55783344CT genotype combinations exhibited a stronger association with CAD risk (AOR = 2.622; 95% CI 1.518-4.526; P = 0.001). Gene-environment combinatorial analyses indicated that the CUBN rs2291521GA, HNF1A rs55783344CT, and LIPC rs17269397AA genotype combination and several clinical factors (fasting blood sugar (FBS), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels) were associated with increased CAD risk. The CUBN rs2291521GA, HNF1A rs55783344CT, and LIPC rs17269397AA genotypes in conjunction with abnormally elevated cholesterol levels increase the risk of developing CAD. This exploratory study suggests that polymorphisms in the CUBN, HNF1A, and LIPC genes can be useful biomarkers for CAD diagnosis and treatment.
本研究旨在通过全外显子组测序（WES）方法鉴定与冠心病（CAD）相关的新型遗传标志物，并确定所选基因多态性与 CAD 患病率之间的任何关联。通过 WES 筛选鉴定与 CAD 易感性相关的 CUBN、HNF1A 和 LIPC 基因多态性。在 452 例 CAD 患者和 421 例对照中，检测了五个基因多态性与 CAD 易感性之间的可能关联。多变量逻辑回归分析表明，CUBN rs2291521GA 和 HNF1A rs55783344CT 基因型与 CAD 相关（GG 与 GA；调整后的优势比 [AOR] = 1.530；95%置信区间 [CI] 1.113-2.103；P = 0.002 和 CC 与 CT；AOR = 1.512；95%CI 1.119-2.045；P = 0.007）。CUBN rs2291521GA 和 HNF1A rs55783344CT 基因型组合与 CAD 风险具有更强的相关性（AOR = 2.622；95%CI 1.518-4.526；P = 0.001）。基因-环境组合分析表明，CUBN rs2291521GA、HNF1A rs55783344CT 和 LIPC rs17269397AA 基因型组合以及一些临床因素（空腹血糖（FBS）、高密度脂蛋白（HDL）和低密度脂蛋白（LDL）水平）与 CAD 风险增加相关。CUBN rs2291521GA、HNF1A rs55783344CT 和 LIPC rs17269397AA 基因型与异常升高的胆固醇水平相结合，增加了患 CAD 的风险。这项探索性研究表明，CUBN、HNF1A 和 LIPC 基因的多态性可以作为 CAD 诊断和治疗的有用生物标志物。
