ASSOCIATION BETWEEN AN ANGIOTENSINOGEN MICROSATELLITE MARKER IN CHILDREN AND CORONARY EVENTS IN THEIR GRANDPARENTS

Background Recently we found that the deletion (D) allele of the inser tion/deletion (I/D) polymorphism of the ACE gene in 404 children was a ssociated with a history of coronary artery disease (CAD) in their gra ndparents. This led us to explore polymorphisms in other genes of the renin-angiotensin system in this same population. Methods and Results We determined the genotypes for three microsatellite markers located n ear or in the angiotensinogen, angiotensin IT (type-1) receptor, and r enin genes in the children and related the allele frequencies to grand parental CAD. We found a significant association between the angiotens inogen marker in children and grandparental CAD (chi(2)=42.2, P=.00001 ) with these children having an excess of the 125-bp and 129-bp allele s (odds ratio, 2.5; 95% confidence interval, 1.7 to 3.7). Greatest gra ndparental risk was when their grandchildren had the 125-bp/125-bp, 12 9-bp/129-bp, or 125-bp/129-bp genotypes (odds ratio, 7.75; 95% confide nce interval, 2.2 to 27). There was no association between the microsa tellites at either the angiotensin II (type-1) receptor (P=.8) or reni n (P=.2) genes in children and grandparental CAD and none between the angiotensinogen and ACE polymorphisms in relation to CAD family histor y. Conclusions This study identifies a significant association between an angiotensinogen marker in children and grandparental CAD. There wa s no association between the microsatellites at either the angiotensin II (type-1) receptor or renin genes and CAD in this population. We co nclude that the angiotensinogen polymorphism as well as the ACE polymo rphism may explain a part of the risk related to a family history of C AD.