This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mahaney, M. C. Articles by VandeBerg, J. L. Search for Related Content PubMed PubMed Citation Articles by Mahaney, M. C. Articles by VandeBerg, J. L. Related Collections Animal models of human disease Risk Factors Lipid and lipoprotein metabolism

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:1134-1141.)
© 1999 American Heart Association, Inc.

Original Contributions

Pleiotropy and Genotype by Diet Interaction in a Baboon Model for Atherosclerosis

A Multivariate Quantitative Genetic Analysis of HDL Subfractions in Two Dietary Environments

Michael C. Mahaney; John Blangero; David L. Rainwater; Glen E. Mott; Anthony G. Comuzzie; Jean W. MacCluer; John L. VandeBerg
Abstract—We investigated dietary effects on pleiotropic relationships among 3 HDL cholesterol (C) subfractions (HDL₁-C, HDL₂-C, and HDL₃-C; levels quantified by gradient gel electrophoresis) for 942 pedigreed baboons (Papio hamadryas) who were fed a basal (Chow) diet and a high cholesterol, saturated fat (HCSF) challenge diet. Using multivariate maximum likelihood methods we estimated heritabilities for all 6 traits, genetic and environmental correlations (_G and _E) between them, and the additive genetic variance of each subfraction's response to the diets. On the Chow diet, genetic correlations between the 3 subfractions were significant, and we observed complete pleiotropy between HDL₁-C and HDL₃-C (_G=-0.81). On the HCSF diet, only the genetic correlation between HDL₁-C and HDL₃-C (_G=-0.61) was significant. Genetic correlations between individual subfractions on the Chow and HCSF diets did not differ significantly from 1.0, indicating that the same additive genes influenced each subfraction's levels regardless of diet. However, the additive genetic variance of response to the diets was highly significant for HDL₁-C and HDL₂-C, but not for HDL₃-C. Similar sets of genes influence variation in the 3 HDL subfractions on the Chow diet, and the same set influences variation in each subfraction on the HCSF diet. However, the expression of genes influencing HDL₁-C and HDL₂-C is altered by the HCSF diet, disrupting the pleiotropy observed between the 3 subfractions on the Chow diet.

Key Words: atherosclerosis risk factors • lipemic response • dietary challenge • animal models • statistical genetics • gradient gel electrophoresis

This article has been cited by other articles:

				D. L. Rainwater, L. A. Cox, J. Rogers, J. L. VandeBerg, and M. C. Mahaney Localization of multiple pleiotropic genes for lipoprotein metabolism in baboons J. Lipid Res., July 1, 2009; 50(7): 1420 - 1428. [Abstract] [Full Text] [PDF]

				J. M Ordovas Genetic influences on blood lipids and cardiovascular disease risk: tools for primary prevention Am. J. Clinical Nutrition, May 1, 2009; 89(5): 1509S - 1517S. [Abstract] [Full Text] [PDF]

				L. A. Cox, S. Birnbaum, M. C. Mahaney, D. L. Rainwater, J. T. Williams, and J. L. VandeBerg Identification of Promoter Variants in Baboon Endothelial Lipase That Regulate High-Density Lipoprotein Cholesterol Levels Circulation, September 4, 2007; 116(10): 1185 - 1195. [Abstract] [Full Text] [PDF]

				D. L. Rainwater, M. C. Mahaney, X. L. Wang, J. Rogers, L. A. Cox, and J. L. VandeBerg Determinants of variation in serum paraoxonase enzyme activity in baboons J. Lipid Res., July 1, 2005; 46(7): 1450 - 1456. [Abstract] [Full Text] [PDF]

				T. A. Demmers, P. J. H. Jones, Y. Wang, S. Krug, V. Creutzinger, and J. E. Heubi Effects of Early Cholesterol Intake on Cholesterol Biosynthesis and Plasma Lipids Among Infants Until 18 Months of Age Pediatrics, June 1, 2005; 115(6): 1594 - 1601. [Abstract] [Full Text] [PDF]