NPR-C gene polymorphism is associated with increased susceptibility to coronary artery disease in Chinese Han population: a multicenter study

// Qin Hu 1 , Qiji Liu 2 , Shasha Wang 1 , Xi Zhen 1 , Zhimian Zhang 3 , Ruijuan Lv 4 , Guihua Jiang 1 , Zhiyong Ma 1 , Hong He 1 , Daqing Li 1 , Xiaoling Liu 1 , Fei Gao 1 , Jifu Li 1 , Li Li 1 , Mei Zhang 1 , Xiaoping Ji 1 , Yuguo Chen 4 , Daowen Wang 5 , Dejia Huang 6 , Aiqun Ma 7 , Wei Huang 8 , Yuxia Zhao 1 , Yaoqin Gong 2 , Cheng Zhang 1 and Yun Zhang 1 1 Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Cardiology, Shandong University Qilu Hospital, Jinan, Shandong, China 2 Department of Medical Genetics, School of Medicine, Key Laboratory of Experimental Teratology, Ministry of Education, Shandong University, Jinan, Shandong, China 3 Medical Examination Center, Shandong University Qilu Hospital, Jinan, Shandong, China 4 Department of Emergency, Shandong University Qilu Hospital, Jinan, Shandong, China 5 Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China 6 Division of Cardiology, Department of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China 7 Department of Cardiology and Periphery Vascular Medicine, The First Affiliated Hospital of Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi, China 8 Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Department of Genetics, Chinese National Human Genome Center, Shanghai, China Correspondence to: Cheng Zhang, email: // Yun Zhang, email: // Keywords : natriuretic peptide receptor C, coronary artery disease, genome-wide association studies, single nucleotide polymorphisms, susceptibility gene, Pathology Section Received : November 24, 2015 Accepted : May 04, 2016 Published : May 13, 2016 Abstract To find a new locus that confers significant susceptibility to CAD in Chinese Han population, a genome-wide association study in 200 “extreme individuals” from a Shandong cohort and a pathway-based candidate gene study from a Shanghai cohort (293 CAD/293 controls) were simultaneously performed. Amongst them, 13 SNPs associated with CAD were selected to conduct validation and replication studies in additional 3363 CAD patients and 3148 controls. A novel locus rs700926 in natriuretic peptide receptor C (NPR-C) was identified in Shandong and Hubei cohorts. Then rs700926 and other nine tag SNPs were genotyped in four geographically different populations (Shandong, Shaanxi, Hubei and Sichuan cohorts), and 6 SNPs (rs700926, rs1833529, rs2270915, rs17541471, rs3792758 and rs696831) showed stronger association with CAD, regardless of single or combined analysis. We further genotyped rs2270915 and 10 additional tag SNPs in a central China cohort and identified rs12697273 and rs10066436 as the loci associated with CAD. All these positive associations remained significant after adjustment for traditional risk factors of CAD. NPR-C gene SNPs significantly contribute to CAD susceptibility in the Chinese Han population.