A study of associations between CUBN, HNF1A, and LIPC gene polymorphisms and coronary artery disease

• Published in: Scientific reports Vol. 10; no. 1; p. 16294
• Main Authors: Park, Han Sung, Kim, In Jai, Kim, Eun Gyo, Ryu, Chang Soo, Lee, Jeong Yong, Ko, Eun Ju, Park, Hyeon Woo, Sung, Jung Hoon, Kim, Nam Keun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2020; Nature Publishing Group
• Subjects: 631/114; 631/208; 692/53; 692/699; Cardiovascular disease; Case-Control Studies; Cholesterol; Coronary artery; Coronary Artery Disease - genetics; Coronary vessels; Female; Gene Frequency - genetics; Gene polymorphism; Genetic markers; Genetic Markers - genetics; Genetic Predisposition to Disease - genetics; Genotypes; Heart diseases; Hepatocyte Nuclear Factor 1-alpha - genetics; High density lipoprotein; Humanities and Social Sciences; Humans; Lipase - genetics; Logistic Models; Low density lipoprotein; Male; Middle Aged; multidisciplinary; Polymorphism, Genetic - genetics; Polymorphism, Single Nucleotide - genetics; Receptors, Cell Surface - genetics; Science; Science (multidisciplinary); Whole Exome Sequencing
• ISSN: 2045-2322; 2045-2322
• 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.