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(Hypertension. 2003;41:854.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Two Loci Affect Angiotensin I–Converting Enzyme Activity in Baboons

Candace M. Kammerer; David L. Rainwater; Jennifer L. Schneider; Laura A. Cox; Michael C. Mahaney; Jeffrey Rogers; Jane F. VandeBerg

From the Department of Human Genetics, University of Pittsburgh (C.M.K.), Penn; Southwest Foundation for Biomedical Research (C.M.K., D.L.R., J.L.S., L.A.C., M.C.M., J.R., J.F.V.), San Antonio, Tex; and Southwest National Primate Research Center (J.R.), San Antonio, Tex

Correspondence to Candace M. Kammerer, Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, A310 Crabtree Hall, 130 De Soto St, Pittsburgh, PA 15261. E-mail ckammerer{at}hgen.pitt.edu

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 (_G) with LDLC response (LDLC_RC) to a high-cholesterol diet (_G=0.30±0.13, P=0.01) but not to LDLC on a basal diet (_G=0.08±0.13). Bivariate genetic analyses indicated that a previously detected QTL for LDLC_RC 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.

Key Words: angiotensin-converting enzyme • cholesterol • diet • genetics • linkage • baboons

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