Genotype-phenotype associations between chymase and angiotensin-converting enzyme gene polymorphisms in chronic systolic heart failure patients.

Abstract

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.

• Authors: Ruthie E Amir, Offer Amir, Hagar Paz, Moran Sagiv, Roi Mor, Michael Sagiv, Basil S Lewis
• Journal: Genetics in medicine : official journal of the American College of Medical Genetics (Genet Med) Vol. 10 Issue 8 Pg. 593-8 (Aug 2008) ISSN: 1530-0366 [Electronic] United States
• PMID: 18641516 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peptidyl-Dipeptidase A
• Chymases

Topics

• Aged
• Chronic Disease
• Chymases (genetics)
• Female
• Genotype
• Heart Failure, Systolic (genetics)
• Humans
• Male
• Middle Aged
• Peptidyl-Dipeptidase A (genetics)
• Phenotype
• Polymorphism, Genetic (genetics)