Genotype-phenotype associations between chymase and angiotensin-converting enzyme gene polymorphisms in chronic systolic heart failure patients.
OBJECTIVE
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.
Amir
Ruthie E
RE
Department of Genetics and Molecular Biology, Zinman College of Physical Education and Sport Sciences at the Wingate Institute, Netanya, Israel. ruthiea@wincol.ac.il
Amir
Offer
O
Paz
Hagar
H
Sagiv
Moran
M
Mor
Roi
R
Sagiv
Michael
M
Lewis
Basil S
BS
D000368:Aged; D002908:Chronic Disease; D053818:Chymases / Q000235:genetics*; D005260:Female; D005838:Genotype; D054143:Heart Failure, Systolic / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*
D007703:Peptidyl-Dipeptidase A; D053818:Chymases