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

TitleGenotype-by-diet effects on co-variation in Lp-PLA2 activity and LDL-cholesterol concentration in baboons fed an atherogenic diet.
Publication TypeJournal Article
Year of Publication2008
AuthorsVinson, A, Mahaney, MC, Diego, VP, Cox, LA, Rogers, J, VandeBerg, JL, Rainwater, DL
JournalJ Lipid Res
Volume49
Issue6
Pagination1295-302
Date Published2008 Jun
ISSN0022-2275
Keywords1-Alkyl-2-acetylglycerophosphocholine Esterase, Animals, Cholesterol, LDL, Dietary Fats, Female, Genetic Predisposition to Disease, Genotype, Male, Papio, Quantitative Trait Loci, Risk Factors
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.

DOI10.1194/jlr.M800020-JLR200
Alternate JournalJ. Lipid Res.
PubMed ID18334716
PubMed Central IDPMC2386906
Grant ListC06 RR-13556 / RR / NCRR NIH HHS / United States
P51 RR-013986 / RR / NCRR NIH HHS / United States
C06 RR017515 / RR / NCRR NIH HHS / United States
C06 RR013556 / RR / NCRR NIH HHS / United States
P01 HL028972 / HL / NHLBI NIH HHS / United States
C06 RR-014578 / RR / NCRR NIH HHS / United States
R01 HL068922 / HL / NHLBI NIH HHS / United States
R01 RR008781 / RR / NCRR NIH HHS / United States
C06 RR-017515 / RR / NCRR NIH HHS / United States
C06 RR014578 / RR / NCRR NIH HHS / United States
R01 RR-008781 / RR / NCRR NIH HHS / United States
P01 HL-028972 / HL / NHLBI NIH HHS / United States
C06 RR015456 / RR / NCRR NIH HHS / United States
R01 HL-068992 / HL / NHLBI NIH HHS / United States
C06 RR-15456 / RR / NCRR NIH HHS / United States
P51 RR013986 / RR / NCRR NIH HHS / United States