Genetic variation of CXCR4 and risk of coronary artery disease: epidemiological study and functional validation of CRISPR/Cas9 system

// Guo Runmin 1 , Jiang Jiamei 1 , Jing Zhiliang 2 , Chen Yonghua 2 , Shi Zhizhou 3 , Tao Guizhou 4 and Liu Shuguang 5 1 Department of Cardiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China 2 Department of Pathology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China 3 Department of Endocrinology and Metabolism, Longgang District People’s Hospital, Shenzhen 518172, China 4 The Third People’s Hospital of Dalian, Dalian, Liaoning 116091, P.R. China 5 Department of Pathology, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong 518033, P.R. China Correspondence to: Liu Shuguang, email: liu_shuguang@aliyun.com Keywords: coronary artery disease; variation; genetic; CXCR4 Received: June 23, 2017      Accepted: October 05, 2017      Epub: December 15, 2017      Published: March 06, 2018 ABSTRACT Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, while coronary artery disease (CAD) account for a large part of CVDs. Vascular CXCR4 could limit atherosclerosis by maintaining arterial integrity. Here, we conducted a population-based, case-control study to evaluate the associations of common genetic variation within the CXCR4 gene (rs2228014, rs117600832, rs2471859, and rs2322864) with CAD risk in a Chinese population. We found that CXCR4 rs2228014 was significantly associated with 1.29-fold increased risk of CAD (A vs G: OR = 1.29; 95% CI = 1.07–1.55; P = 0.007). The subjects with genotype AA (OR = 1.98; 95% CI = 1.03–3.81; P = 0.041) and AG (OR = 1.27; 95% CI = 1.02–1.58; P = 0.030) have higher risk of CAD, compared with those with genotype GG. Furthermore, both in the CAD patients with diabetes and those without diabetes, rs2228014 was significantly associated with increased risk of CAD ( P < 0.05). Additionally, we also validated the significant association for rs2322864 (C vs T: OR = 1.20; 95% CI = 1.00–1.44; P = 0.046). Knockout of CXCR4 gene could significantly impair the capacity of cholesterol efflux ( P < 0.01). These findings strongly suggest that CXCR4 polymorphisms might contribute to CAD susceptibility, and the exact biological mechanism awaits further research.