ANGIOTENSIN-CONVERTING ENZYME GENOTYPE IN CHILDREN AND CORONARY EVENTS IN THEIR GRANDPARENTS

Background It has been suggested that the insertion/deletion (I/D) pol ymorphism of the angiotensin-converting enzyme (ACE) gene is an indepe ndent 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 his tory of myocardial infarction. Methods and Results We explored the dis tribution of the ACE genotype in 404 school children, aged 6 to 13 yea rs, and related the distribution to the number of their grandparents w ho had had vascular events. We found a significant association between the number of grandparents who had had coronary events and the ACE ge notype (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% confidenc e interval=0.62-3.25]) genotypes compared with I/I genotypes. In addit ion, 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 pr oving to be more predictive than lipoprotein(a) levels. Conclusions We conclude that the I/D polymorphism of the ACE gene is an important in dependent risk factor for coronary artery disease and is more predicti ve that lipoprotein(a). The I/D polymorphism is not only associated wi th 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 li poprotein(a) is indicated.