PURPOSE: Angiotensin II, which plays a crucial role in the myocardial remodeling process of heart failure, is generated via the angiotensin-converting enzyme and chymase pathways. We studied angiotensin-converting enzyme and chymase-1 polymorphisms in patients with systolic heart failure and the correlation with clinical status and left ventricular function. METHODS: We genotyped 195 patients with heart failure and systolic left ventricular dysfunction (ejection fraction <40%) for angiotensin-converting enzyme insertion (I)/deletion (D) and chymase-1 (-1903G/A) polymorphisms. Heart failure etiology and patients' clinical manifestations were analyzed in relation to genotype subtypes. RESULTS: The chymase-1 -1903 GG genotype was associated with a nonischemic heart failure etiology (chi = 6.67, P = 0.009). In the group of heart failure patients, the odds ratio of chymase-1 GG genotype having a nonischemic etiology was 2.48 (95% CI 1.23-5.00). The chymase-1 GG genotype was associated with lower ejection fraction (P = 0.005). Conversely, the angiotensin-converting enzyme D allele had no detectable impact on systolic heart failure phenotype. CONCLUSIONS: In patients with chronic systolic heart failure, the chymase-1 polymorphism was related to nonischemic etiology of heart failure. Patients homozygous for the G allele had a significantly greater reduction in systolic left ventricular function.
PURPOSE:Angiotensin II, which plays a crucial role in the myocardial remodeling process of heart failure, is generated via the angiotensin-converting enzyme and chymase pathways. We studied angiotensin-converting enzyme and chymase-1 polymorphisms in patients with systolic heart failure and the correlation with clinical status and left ventricular function. METHODS: We genotyped 195 patients with heart failure and systolic left ventricular dysfunction (ejection fraction <40%) for angiotensin-converting enzyme insertion (I)/deletion (D) and chymase-1 (-1903G/A) polymorphisms. Heart failure etiology and patients' clinical manifestations were analyzed in relation to genotype subtypes. RESULTS: The chymase-1 -1903 GG genotype was associated with a nonischemic heart failure etiology (chi = 6.67, P = 0.009). In the group of heart failurepatients, the odds ratio of chymase-1 GG genotype having a nonischemic etiology was 2.48 (95% CI 1.23-5.00). The chymase-1 GG genotype was associated with lower ejection fraction (P = 0.005). Conversely, the angiotensin-converting enzyme D allele had no detectable impact on systolic heart failure phenotype. CONCLUSIONS: In patients with chronic systolic heart failure, the chymase-1 polymorphism was related to nonischemic etiology of heart failure. Patients homozygous for the G allele had a significantly greater reduction in systolic left ventricular function.
Authors: Ewa Orlowska-Baranowska; Jaroslaw Gora; Rafal Baranowski; Patrycjusz Stoklosa; Lucja Gadomska vel Betka; Ewa Pedzich-Placha; Malogrzata Milkowska; Marta K Koblowska; Tomasz Hryniewiecki; Zbigniew Gaciong; Grzegorz Placha Journal: PLoS One Date: 2014-05-13 Impact factor: 3.240