title: Genotype-by-diet effects on co-variation in Lp-PLA2 activity and LDL-cholesterol concentration in baboons fed an atherogenic diet.
abstract: Both lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) 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-PLA(2) 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-PLA(2) 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-PLA(2) activity and LDL-C levels in the HCHF diet. We additionally found significant evidence of genetic variance in response to diet for Lp-PLA(2) 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-PLA(2) activity and LDL-C concentration.
authors.affiliation: Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX, USA. avinson@sfbrgenetics.org
authors.forename: Amanda
authors.initials: A
authors.lastname: Vinson
authors.forename: Michael C
authors.initials: MC
authors.lastname: Mahaney
authors.forename: Vince P
authors.initials: VP
authors.lastname: Diego
authors.forename: Laura A
authors.initials: LA
authors.lastname: Cox
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Rogers
authors.forename: John L
authors.initials: JL
authors.lastname: VandeBerg
authors.forename: David L
authors.initials: DL
authors.lastname: Rainwater
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D000818:Animals; D008078:Cholesterol, LDL / Q000097:blood*; D004041:Dietary Fats / Q000008:administration & dosage*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D008297:Male; D010215:Papio; D040641:Quantitative Trait Loci; D012307:Risk Factors
chemical_list: D008078:Cholesterol, LDL; D004041:Dietary Fats; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase