A Common NOS1AP Genetic Polymorphism, rs12567209 G>A, Is Associated With Sudden Cardiac Death in Patients With Chronic Heart Failure in the Chinese Han Population

• Published in: Journal of cardiac failure 2014-04, Vol.20 (4), p.244-251
• Main Authors: Liu, Xiaoyan, PhD, Pei, Juanhui, MD, PhD, Hou, Cuihong, MD, Liu, Na, PhD, Chu, Jianmin, MD, MSc, Pu, Jielin, MD, PhD, Zhang, Shu, MD, PhD, FHRS, FESC
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Aged; Alleles; Cardiovascular; Cause of Death - trends; China - epidemiology; chronic heart failure; Death, Sudden, Cardiac - etiology; DNA - genetics; Electrocardiography; Ethnic Groups - genetics; Female; Follow-Up Studies; genetic association; Genotype; Heart Failure - complications; Heart Failure - ethnology; Heart Failure - genetics; Humans; Male; Middle Aged; NOS1AP; Polymerase Chain Reaction; Polymorphism, Genetic; Prospective Studies; QTc interval; Risk Factors; sudden cardiac death; Survival Rate - trends
• ISSN: 1071-9164; 1532-8414
• DOI: 10.1016/j.cardfail.2014.01.006

Abstract Background Variants in NOS1AP associated with cardiac repolarization and sudden cardiac death (SCD) in coronary artery disease have been reported. Whether they are related to mortality and QTc interval in chronic heart failure (CHF) has not been investigated. Methods and Results A total of 1,428 patients with CHF and 480 control subjects were genotyped for 6 SNPs of NOS1AP, and the genetic associations with mortality as well as QTc interval were analyzed. During a median follow-up period of 52 months, 467 patients (32.70%) died, of which deaths 169 (36.19%) were SCD. The A allele of rs12567209 was associated with greater risk of all-cause death and SCD (hazard ratio [HR] 1.381, 95% confidence interval [CI] 1.124–1.698 [ P  = .002], and HR 1.645, 95% CI 1.184–2.287 [ P  = .003], respectively). After adjusting for other risk factors, significant differences remained (HR 1.309, 95% CI 1.054–1.624 [ P  = .015], and HR 1.601, 95% CI 1.129–2.271 [ P  = .008]). The A allele was also associated with prolongation of QTc interval by 4.04 ms in the entire population ( P  = .026). Conclusions The A allele of rs12567209 in NOS1AP may serve as an independent predictor of all-cause death and SCD in patients with CHF, it is also associated with prolonged QTc interval in the Chinese Han population.