The Role of Angiotensin‐Converting Enzyme Polymorphism in Congestive Heart Failure

Abstract

Angiotensin‐converting enzyme (ACE) is a zinc metallopeptidase, with primary known functions of converting angiotensin I into the vasoactive and aldosterone‐stimulating peptide angiotensin II and inactivating bradykinin. There is high variability among individuals in ACE concentrations, mainly due to the presence of a genetic polymorphism. The ACE gene has, in fact, insertion/deletion polymorphism in intron 16, consisting of a 287‐base pair Alu repeat sequence, with three genotypes: insertion polymorphism, insertion/deletion polymorphism, and deletion polymorphism. The genetic effect accounts for 47% of the total variance of serum ACE. The determination of this polymorphism has allowed researchers to study the implications of the ACE gene in many case‐control studies of cardiovascular disease, including myocardial infarction and hypertrophic and dilated cardiomyopathy. We review the current knowledge about the ACE gene polymorphism and its implications in heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Interpretation of the results of studies about the role of this polymorphism are controversial. The repetition of epidemio‐genetic studies and the creation of adequate experimental studies will help to definitively establish the pathogenetic role of the permanent increase in ACE expression associated with the deletion polymorphism genotype.

Angiotensin-converting enzyme gene insertion/deletion polymorphism studies in Asian Indian pregnant women biochemically identifies gestational diabetes mellitus

“…3 Table 6 summarizes previous studies that are related to ACE genotype associations. [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] In the present study, we investigated the possible association of ACE I/D polymorphisms with the development of GDM among selected individuals from the Asian Indian population. The study was carried out between two groups (GDM cases and non-GDM subjects) and showed significant differences with respect to age, weight and PPBG.…”

Genetics and pharmacogenetics in heart failure

“…ACE is involved in both vascular function as well as ventricular muscle growth [15]. Previous studies have estimated that genetic variation accounts for approximately 50% of the total variance in serum ACE levels in humans [16]. The most prominent polymorphism of the gene that encodes ACE is a 287 bp insertion/deletion segment (I/D) in intron 16.…”

Cardiovascular Nursing on Human Genomics: What Do Cardiovascular Nurses Need to Know About Congestive Heart Failure?

“…In the last 5 years, the effects of a common variation in the DNA sequence, single nucleotide polymorphisms (SNPs) in candidate genes in HF have been reviewed and summarized by several authors. [16][17][18][19][20] These reviews suggest that there is evidence that genes play a role in the pathophysiology of HF. Most studies report that many SNPs may have a modest effect on HF outcomes.…”

“…However, standardized pharmacologic treatment leads to marked variability in clinical outcome. 18,23 Recently, pharmacogenetic data for b-blockers in patients with HF and potential implications of b-blocker pharmacogenetics for HF patients have also been summarized by several authors. 24,25 It is suggested that the ADRB 1 Ar-g389Gly polymorphism might predict responsiveness to b 1 -adrendric receptor agonists and blockers: individuals homozygous for the Arg389 polymorphism may be good responders, while those homozygous for Gly389 may be poor or nonresponders.…”