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Background: Controversy exists about the presence of an association between myocardial infarction (MI) and the deletion allele of the insertion-deletion (I/D) polymorphism of the angiotensin-1 converting enzyme (ACE), particularly in patients considered to be at "low risk". A large study was needed to test these hpothesised associations reliably. Methods: Comparison of 4629 MI cases and 5934 controls. Cases were UK males aged 30-54 years and females aged 30-64 years recruited on presentation to hospital with confirmed MI. Controls were aged 30-64 years with no history of cardiovascular disease, but were siblings or children of MI survivors, or spouses of such relatives. Findings: The DD genotype was found in 1359 (29.4%) of the MI cases and in 1637 (27.6%) of the controls, yielding a risk ratio of 1.10 (95% Cl 1.00 - 1.21). The association between MI and the DD genotype did not appear to be stronger in a subgroup defined as "low risk" by apolipoprotein B and BMI criteria (RR 1.04; 95% Cl 0.87 - 1.24). Nor was the ACE I/D genotype predictive of subsequent survival. Interpretation: This study involved four times as many cases as any previously reported study of this question, but did not confirm the existence of any substantial association. Taking these results together with those of all previously published studies in an updated meta-analysis, it is concluded that the relative risk of MI associated with the DD genotype lies between 1.0 and 1.1. These findings illustrate the need for some such studies of candidate genes to involve much larger populations than is currently customary.


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