A METAANALYSIS 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 th e presence (insertion [I]) or absence (deletion [D]) within intron 16 of a 287-basepair alu repeat sequence, resulting in three genotypes (D D and II homozygotes and ID bet erozygotes). In 1992, the DD genotype was reported to be associated with an increased risk of myocardial inf arction (MI). Subsequent studies have produced conflicting findings. T o further evaluate the association of the ACE I/D genotype with MI ris k, we carried out a meta-analysis of all the published studies. Method s and Results In total, 15 studies containing 3394 MI cases and 5479 c ontrol subjects were analyzed. The overall distribution of genotypes i n 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 an d ID, and 1.09 (95% CI, 0.96, 1.23) for ID and II. The relative risk a ppeared to be increased in Japanese populations (2.55; 95% CI, 1.75, 3 .70). Conclusions Within the limitations of the available data, the me ta-analysis therefore supports an association of the ACE D allele with MI risk and strengthens the justification for further evaluation in a ppropriately powered studies.