Angiotensin-converting enzyme gene polymorphism and premature coronary heart disease

Since the initial report of the association of the deletion/insertion (D/I) polymorphism in the gene for angiotensin-converting enzyme (ACE) with myocardial infarction (MI), there has been considerable controversy. Some have found the D allele to be associated with MI, coronary heart disease (CHD) or other cardiac pathology, while others have not. In the present study 713 consecutive patients, < 50 years of age, documented prospectively with angiographic CHD (> 50% diameter stenosis of at least one coronary artery), with or without MI, were studied, along with 688 community control subjects, also < 50 years of age, selected randomly from the electoral rolls and without a history of CHD or MI. Genotyping was done by standard methods. Most of the subjects in both groups were Anglo-Celtic Caucasians (547 in the CHD group and 642 in the community group), and the report concerns primarily these subjects. ACE genotype distributions were not different between the Caucasian community control group and the CHD or the MI subgroups; the odds ratios and 95% confidence limits for the CHD group were 0.96 (0.73-1.27) for the D allele and 1.02 (0.80-1.31) for D homozygotes; for the MI group these values were 1.00 (0.83-1.20) and 0.99 (0.74-1.32) respectively. This negative result was supported in multivariate analysis accounting for conventional risk factors. There was a significant racial difference in ACE genotypes between Caucasians, Asians and Australian Aborigines in the CHD group (P < 0.001); for example, in this group, 158 of 540 (29%) Caucasians had the DD genotype compared with eight of 84 (10%) Aboriginals (P < 0.001) and six of 59 (10%) Asians (P = 0.002). Failure to account for such racial differences would have led to erroneous conclusions. In conclusion, we found no evidence that the D/I ACE gene polymorphism plays a role in the development of CHD or MI at an early age in a Western Australian Caucasian population. While this result refers uniquely to premature CHD and MI, and could be population specific, it is in general agreement with recent meta-analysis of the larger previous studies.