Submitted on January 15, 2008
Revised on March 10, 2008
Accepted on March 10, 2008
Genotype-by-diet effects on co-variation in Lp-PLA2 activity and LDL cholesterol concentration in baboons fed an atherogenic diet
Amanda Vinson, Michael C. Mahaney, Vince P. Diego, Laura A. Cox, Jeffrey Rogers, John L. VandeBerg, and David L. Rainwater
Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78245
Corresponding Author: 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 QTL corresponding to 2p24.3—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 (LOD=3.13, genome-wide P=0.019) corresponding to 19q12—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 co-variation 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 co-variation in Lp-PLA2 activity and LDL-C concentration.
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