Key result
In 622 baboons, two loci were found to affect ACE activity, with one locus showing significant pleiotropic effects on LDL cholesterol response to a high-cholesterol diet (P=0.025).
Observational (n=622)
Effect estimate: rhoG 0.30
p-value: p=0.01
Identified two genetic loci affecting ACE activity in baboons, one of which also influences LDL cholesterol response to diet, potentially explaining inconsistencies in ACE-CVD association studies.
No immediate clinical implications; extends animal models of ACE-lipid pleiotropy and leaves open human translation.
Serum LDL cholesterol (LDLC) concentrations and ACE activities are risk factors for the development of cardiovascular disease (CVD). However, the relationship between ACE and CVD susceptibility, and possible mechanisms of action, is controversial. With data on 622 pedigreed baboons, we used statistical genetic methods to determine the mode of inheritance of ACE activities and its relationship to LDLC on different diets. ACE activity was moderately heritable, and quantitative trait linkage analyses detected a quantitative trait locus (QTL) for ACE activity on the baboon homolog of human chromosome 17 (near the ACE structural locus, maximum multipoint lod=7.5, genomic P=0.000003). Bivariate analyses revealed that ACE activity was genetically correlated (rhoG) with LDLC response (LDLCRC) to a high-cholesterol diet (rhoG=0.30+/-0.13, P=0.01) but not to LDLC on a basal diet (rhoG=0.08+/-0.13). Bivariate genetic analyses indicated that a previously detected QTL for LDLCRC had significant (P=0.025) pleiotropic effects on ACE activity levels and accounted for the genetic correlation. Therefore, we have detected 2 putative loci that affect ACE activity in baboons, one of which also affects LDLC dietary response. The existence of at least 2 genes that affect ACE activity, one of which is diet-responsive, may help explain the lack of consistency among studies of the relationship between ACE and CVD.
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Kammerer et al. (2003) conducted an observational in Cardiovascular disease risk factors (animal model) (n=622). High-cholesterol diet and genetic loci vs. Basal diet was evaluated on Genetic correlation between ACE activity and LDLC response (rhoG 0.30, p=0.01). In 622 baboons, two loci were found to affect ACE activity, with one locus showing significant pleiotropic effects on LDL cholesterol response to a high-cholesterol diet (P=0.025).
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