A prospective evaluation of the angiotensin-converting enzyme D/I polymorphism and left ventricular remodeling in the 'Healing and Early Afterload Reducing Therapy' study.
The D/I (deletion, D, insertion, I) polymorphism of the angiotensin-converting enzyme (ACE) gene has been extensively studied for its association with a number of cardiovascular and other disease states. However, its potential association with differential clinical efficacy of ACE inhibitors (ACE-I) administered to patients who had suffered a myocardial infarction (MI), i.e. the prevention of left ventricular (LV) remodeling, has so far not been specifically studied. The aim of the study was to investigate whether the D/I polymorphism of the ACE gene is associated with the incidence of post-MI LV remodeling in patients drawn from the 'Healing and Early Afterload Reducing Therapy' (HEART) Study. The ACE D/I polymorphism was characterized by the polymerase chain reaction (PCR) in 265 subjects from the 'Healing and Early Afterload Reducing Therapy' Study, a double-blind, placebo-controlled trial with the objective of determining whether early or delayed administration of the ACE-I, ramipril, in patients with acute anterior wall MI would be optimal in reducing LV enlargement. Selected frequencies for the ACE D and I alleles were 0.59 and 0.41 (placebo-high dose group), 0.56 and 0.44 (low dose-low dose group), and, 0.60 and 0.40 (high dose-high dose group), respectively. All observed genotype frequencies were in Hardy-Weinberg equilibrium. There was no evidence for an association between genotype and outcome regarding LV size or function, nor with the initial blood pressure response after ACE-I administration (adjusted for covariates). Our data provide no evidence for an association of the ACE D/I polymorphism with the risk of LV remodeling post-MI in the presence of ACE-I therapy, and therefore do not suggest that differential clinical efficacy of ACE-inhibitors is related to this genetic marker.
Zee
R Y L
RY
Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215-1204, USA. rzee@rics.bwh.harvard.edu
Solomon
S D
SD
Ajani
U A
UA
Pfeffer
M A
MA
Lindpaintner
K
K
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D004562:Electrocardiography; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D017257:Ramipril / Q000627:therapeutic use; D016896:Treatment Outcome; D020257:Ventricular Remodeling
D000806:Angiotensin-Converting Enzyme Inhibitors; D005819:Genetic Markers; D007703:Peptidyl-Dipeptidase A; D017257:Ramipril