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Journal of Lipid Research, Vol. 49, 1295-1302, June 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Genotype-by-diet effects on co-variation in Lp-PLA₂ activity and LDL-cholesterol concentration in baboons fed an atherogenic diet^*

Amanda Vinson^1,*, Michael C. Mahaney^*,, Vince P. Diego^*, Laura A. Cox^*,, Jeffrey Rogers^*,, John L. VandeBerg^*, and David L. Rainwater^*

^* Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX
Southwest National Primate Research Center, San Antonio, TX

^* This study was made possible by research grants from the National Institutes of Health (P01 HL-028972, R01 HL-068922, R01 RR-008781); a base grant from the National Center of Research Resources (NCRR) to the Southwest National Primate Research Center (SNPRC; P51 RR-013986); and was conducted in facilities constructed with support from NCRR Research Facilities Improvement Program Grants (C06 RR-014578, C06 RR-13556, C06 RR-15456, C06 RR-017515).

Published, JLR Papers in Press, March 11, 2008.

¹ To whom correspondence should be addressed. e-mail: avinson{at}sfbrgenetics.org

Both lipoprotein-associated phospholipase A₂ (Lp-PLA₂) activity, a biomarker of inflammation, and concentration of its primary associated lipoprotein, LDL, are correlated with adverse coronary outcomes. We previously reported a quantitative trait locus (QTL) corresponding to HSA2p24.3–p23.2 with pleiotropic effects on Lp-PLA₂ activity and LDL-cholesterol (LDL-C) concentration in baboons fed a basal diet. Here, our goal was to locate pleiotropic QTLs influencing both traits in the same baboons fed a high-cholesterol, high-fat (HCHF) diet, and to assess whether shared genetic effects on these traits differ between diets. We assayed Lp-PLA₂ activity and LDL-C concentration in 683 baboons fed the HCHF diet. We used a bivariate maximum likelihood-based variance components approach in whole-genome linkage screens to locate a QTL [logarithm of odds (LOD) = 3.13, genome-wide P = 0.019] corresponding to HSA19q12–q13.2 with pleiotropic effects on Lp-PLA₂ activity and LDL-C levels in the HCHF diet. We additionally found significant evidence of genetic variance in response to diet for Lp-PLA₂ activity (P = 0.0017) and for LDL-C concentration (P = 0.00001), revealing a contribution of genotype-by-diet interaction to covariation in these two traits. We conclude that the pleiotropic QTLs detected at 2p24.3–p23.2 and 19q12–q13.2 on the basal and HCHF diets, respectively, exert diet-specific effects on covariation in Lp-PLA₂ activity and LDL-C concentration.

Supplementary key words lipoprotein-associated phospholipase A₂ • genotype-by-diet interaction • atherosclerosis • pleiotropy • baboon

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