| Abstract: | AIM: 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-17 A in heart failure. Therefore,we investigated whether common polymorphisms of genes IL17 A and IL17RA( coding interleukin17 receptor A) gene contribute to genetic predisposition to heart failure and adverse clinical outcomes associated with it. METHODS AND RESULTS: A total of 1713 adults patients with congestive heart failure and 1713 age- and sex-matched controls were genotyped for promoter SNPs,rs2275913 and rs8193037 in IL17 A and rs4819554 in IL17 RA,to assess the relationship between individual SNPs and the risk of congestive heart failure. Results showed that rs8193037 in IL17 A was associated with the risk of congestive heart failure(P 0. 01) after adjustment for multiple cardiovascular risk factors including age,sex,smoking status,diabetes,hypertension and dyslipidemia. This association was evident in both ischemic and non-ischemic heart failure( P 0. 05). Furthermore,prospective follow-up of 12. 7 months for the occurrence of adverse clinical outcomes showed that rs4819554 in IL17 RA was significantly associated with cardiovascular mortality( P 0. 05) after adjustments for multiple cardiovascular risk factors and New York Heart Association functional class. CONCLUSION: This study demonstrated associations of rs8193037 in the promoter of IL17 A with the risk of congestive heart failure,and of rs4819554 in the promoter of IL17 RA 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. |
