Angiotensin-Converting Enzyme Genotype in Children and Coronary Events in Their Grandparents

BACKGROUND: It has been suggested that the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is an independent risk factor for coronary artery disease. The D/D genotype, which is associated with higher levels of circulating ACE than the I/D or I/I genotype, has been found significantly more frequently in patients with myocardial infarction and also in individuals with a parental history of myocardial infarction. METHODS AND RESULTS: We explored the distribution of the ACE genotype in 404 school children, aged 6 to 13 years, and related the distribution to the number of their grandparents who had had vascular events. We found a significant association between the number of grandparents who had had coronary events and the ACE genotype (P = .01). In children with two or more grandparents who had had coronary events, there was an excess of both D/D (odds ratio = 2.8 [95% confidence interval = 1.16-6.56]) and I/D (odds ratio = 1.4 [95% confidence interval = 0.62-3.25]) genotypes compared with I/I genotypes. In addition, there was an association between the ACE genotype and lipoprotein(a) levels in children (P = .07). Both the ACE genotype and lipoprotein(a) were found to contribute significantly (P = .0042) and independently to family history of coronary artery disease, with the ACE genotype proving to be more predictive than lipoprotein(a) levels. CONCLUSIONS: We conclude that the I/D polymorphism of the ACE gene is an important independent risk factor for coronary artery disease and is more predictive that lipoprotein(a). The I/D polymorphism is not only associated with a parental history of myocardial infarction but also with coronary artery disease in second-degree relatives. A further study to explore the relation between the I/D polymorphism and circulating levels of lipoprotein(a) is indicated.