A Meta-analysis of the Association of the Deletion Allele of the Angiotensin-Converting Enzyme Gene With Myocardial Infarction

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.