August 15, 1996Circulation419 citations
A Meta-analysis of the Association of the Deletion Allele of the Angiotensin-Converting Enzyme Gene With Myocardial Infarction
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Key Result
The ACE DD genotype was associated with an increased risk of myocardial infarction compared to ID/II genotypes (OR 1.26; 95% CI 1.15-1.39; P<0.0001).
Study Design
Type
Meta-Analysis (n=8,873)
Multicenter
Yes
Structured PICO
Does the ACE gene DD genotype increase the risk of myocardial infarction compared to ID/II genotypes?
P
Population
Meta-analysis of 15 studies comprising 8,873 individuals (3,394 MI cases and 5,479 controls) evaluating the association of the ACE I/D genotype with myocardial infarction.
E
Exposure
ACE gene DD genotype
C
Comparator
ACE gene ID/II genotypes
O
Outcome
Myocardial infarctionhard clinical
This meta-analysis demonstrates a significant association between the ACE gene DD genotype and an increased risk of myocardial infarction.
Main Result
Odds Ratio: 1.26 (95% CI 1.15–1.39)
p-value: p=<.0001
Abstract
BACKGROUND: The ACE gene is characterized by a polymorphism based on the presence (insertion I) or absence (deletion D) within intron 16 of a 287-basepair alu repeat sequence, resulting in three genotypes (DD and II homozygotes and ID heterozygotes). In 1992, the DD genotype was reported to be associated with an increased risk of myocardial infarction (MI). Subsequent studies have produced conflicting findings. To further evaluate the association of the ACE I/D genotype with MI risk, we carried out a meta-analysis of all the published studies. METHODS AND RESULTS: In total, 15 studies containing 3394 MI cases and 5479 control subjects were analyzed. The overall distribution of genotypes in the control subjects was 22.7% II, 49.0% ID, and 28.3% DD. The mean odds ratio for MI for DD versus ID/II genotypes across all studies was 1.26 (95% CI, 1.15, 1.39; P < .0001). Pairwise odds ratios were 1.36 (95% CI, 1.19, 1.55) for DD and II, 1.24 (95% CI, 1.11, 1.38) for DD and ID, and 1.09 (95% CI, 0.96, 1.23) for ID and II. The relative risk appeared to be increased in Japanese populations (2.55; 95% CI, 1.75, 3.70). CONCLUSIONS: Within the limitations of the available data, the meta-analysis therefore supports an association of the ACE D allele with MI risk and strengthens the justification for further evaluation in appropriately powered studies.