Sandip Chaugai, Tan Lun, Huang Jin, Li Qing, Ni Li, Cianflone Katherine, Wang Dao Wen
Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China Centre de Recherche Institut Universitaire de Cardiologie & Pneumologie de Québec, Université Laval, QC, Canada Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Medicine (Baltimore). 2016 Jul;95(27):e4105. doi: 10.1097/MD.0000000000004105.
Heart failure is characterized by immune activation leading to production and release of proinflammatory cytokines. Interleukin 17A (IL-17A) is a proinflammatory cytokine and multiple lines of evidence from animal and human studies suggest crucial roles of IL-17A in heart failure. Therefore, we investigated whether common polymorphisms of genes IL17A and IL17RA (coding interleukin 17 receptor A) contribute to genetic predisposition to heart failure and adverse clinical outcomes associated with it.A total of 1713 adult patients with congestive heart failure and 1713 age- and sex-matched controls were genotyped for promoter single nucleotide polymorphisms (SNPs), rs2275913 and rs8193037 in IL17A and rs4819554 in IL17RA, to assess the relationship between individual SNPs and the risk of congestive heart failure. Results showed that rs8193037 in IL17A was associated with the risk of congestive heart failure (odds ratio [OR] = 0.76; 95% confidence interval [CI] 0.63-0.90, adjusted P = 0.002) after adjustment for multiple cardiovascular risk factors including age, sex, smoking status, diabetes, hypertension, and dyslipidemia. This association was evident in both ischemic and nonischemic heart failure (P = 0.005 and P = 0.05, respectively). Furthermore, prospective follow-up of 12.7 months for the occurrence of adverse clinical outcomes showed that rs4819554 in IL17RA was significantly associated with cardiovascular mortality (hazard ratio [HR] = 1.28; 95% CI = 1.02-1.59, adjusted P = 0.03) after adjustments for multiple cardiovascular risk factors and New York Heart Association functional class.This study demonstrated associations of rs8193037 in the promoter of IL17A with the risk of congestive heart failure, and of rs4819554 in the promoter of IL17RA with the risk of cardiovascular mortality in patients with congestive heart failure. These data lend further support to the notion that immune activation and genetic polymorphisms contribute to heart failure pathogenesis and progression.
心力衰竭的特征是免疫激活，导致促炎细胞因子的产生和释放。白细胞介素17A（IL-17A）是一种促炎细胞因子，来自动物和人体研究的多条证据表明IL-17A在心力衰竭中起关键作用。因此，我们研究了IL17A和IL17RA基因（编码白细胞介素17受体A）的常见多态性是否会导致心力衰竭的遗传易感性以及与之相关的不良临床结局。对总共1713例充血性心力衰竭成年患者和1713例年龄及性别匹配的对照进行基因分型，检测IL17A中的启动子单核苷酸多态性（SNP）rs2275913和rs8193037以及IL17RA中的rs4819554，以评估各个SNP与充血性心力衰竭风险之间的关系。结果显示，在对包括年龄、性别、吸烟状况、糖尿病、高血压和血脂异常在内的多种心血管危险因素进行调整后，IL17A中的rs8193037与充血性心力衰竭风险相关（比值比[OR]=0.76；95%置信区间[CI]0.63-0.90，校正P=0.002）。这种关联在缺血性和非缺血性心力衰竭中均很明显（分别为P=0.005和P=0.05）。此外，对不良临床结局发生情况进行12.7个月的前瞻性随访显示，在对多种心血管危险因素和纽约心脏协会心功能分级进行调整后，IL17RA中的rs4819554与心血管死亡率显著相关（风险比[HR]=1.28；95%CI=1.02-1.59，校正P=0.03）。本研究证明了IL17A启动子中的rs8193037与充血性心力衰竭风险相关，以及IL17RA启动子中的rs4819554与充血性心力衰竭患者的心血管死亡风险相关。这些数据进一步支持了免疫激活和基因多态性参与心力衰竭发病机制和进展的观点。
