Title | Genotype-by-diet effects on co-variation in Lp-PLA2 activity and LDL-cholesterol concentration in baboons fed an atherogenic diet. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Vinson, A, Mahaney, MC, Diego, VP, Cox, LA, Rogers, J, VandeBerg, JL, Rainwater, DL |
Journal | J Lipid Res |
Volume | 49 |
Issue | 6 |
Pagination | 1295-302 |
Date Published | 2008 Jun |
ISSN | 0022-2275 |
Keywords | 1-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. |
DOI | 10.1194/jlr.M800020-JLR200 |
Alternate Journal | J Lipid Res |
PubMed ID | 18334716 |
PubMed Central ID | PMC2386906 |
Grant List | C06 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 P51 RR013986 / RR / NCRR NIH HHS / United States R01 HL-068992 / HL / NHLBI NIH HHS / United States C06 RR-15456 / RR / NCRR NIH HHS / United States |
Genotype-by-diet effects on co-variation in Lp-PLA2 activity and LDL-cholesterol concentration in baboons fed an atherogenic diet.
Similar Publications
DNA Methylation-Derived Immune Cell Proportions and Cancer Risk in Black Participants. Cancer Res Commun. 2024;4(10):2714-2723. | .
Whole genomes of Amazonian uakari monkeys reveal complex connectivity and fast differentiation driven by high environmental dynamism. Commun Biol. 2024;7(1):1283. | .
Rare variant contribution to the heritability of coronary artery disease. Nat Commun. 2024;15(1):8741. | .