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 insertion/deletion (I/D) polymorphism of the ACE gene in 404 children was associated with a history of coronary artery disease (CAD) in their grandparents. 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 near or in the angiotensinogen, angiotensin II (type-1) receptor, and renin genes in the children and related the allele frequencies to grandparental CAD. We found a significant association between the angiotensinogen marker in children and grandparental CAD (chi2 = 42.2, P = .00001) with these children having an excess of the 125-bp and 129-bp alleles (odds ratio, 2.5; 95% confidence interval, 1.7 to 3.7). Greatest grandparental risk was when their grandchildren had the 125-bp/125-bp, 129-bp/129-bp, or 125-bp/129-bp genotypes (odds ratio, 7.75; 95% confidence interval, 2.2 to 27). There was no association between the microsatellites at either the angiotensin II (type-1) receptor (P = .8) or renin (P = .2) genes in children and grandparental CAD and none between the angiotensinogen and ACE polymorphisms in relation to CAD family history. CONCLUSIONS: This study identifies a significant association between an angiotensinogen marker in children and grandparental CAD. There was no association between the microsatellites at either the angiotensin II (type-1) receptor or renin genes and CAD in this population. We conclude that the angiotensinogen polymorphism as well as the ACE polymorphism may explain a part of the risk related to a family history of CAD.