Pleiotropy and genotype by diet interaction in a baboon model for atherosclerosis - A multivariate quantitative genetic analysis of HDL subfractions in two dietary environments

We investigated dietary effects on pleiotropic relationships among 3 HDL ch olesterol (C) subfractions (HDL1-C, HDL2-C, and HDL3-C; levels quantified b y gradient gel electrophoresis) for 942 pedigreed baboons (Papio hamadryas) who were fed a basal (Chow) diet and a high cholesterol, saturated fat (HC SF) challenge diet. Using multivariale maximum likelihood methods we estima ted heritabilities for all 6 traits, genetic and environmental correlations (p(G) and p(E)) between them, and the additive genetic variance of each su bfraction's response to the diets. On the Chow diet, genetic correlations b etween the 3 subfractions were significant, and we observed complete pleiot ropy between HDL1-C and HDL3-C (p(G)=-0.81). On the HCSF diet, only the gen etic correlation between HDL1-C and HDL5-C (p(G)=-0.61) was significant. Ge netic correlations between individual subfractions on the Chow and HCSF die ts did not differ significantly from 1.0, indicating that the same additive genes influenced each subfraction's levels regardless of diet. However, th e additive genetic variance of response to the diets was highly significant for HDL1-C and HDL2-C, but not or HDL3-C. Similar sets of genes influence variation in the 3 HDL subfractions on the Chow diet, and the same set infl uences variation in each subfraction on the HCSF diet. However, the express ion of genes influencing HDL2-C and HDL2-C is altered by the HCSF diet, dis rupting the pleiotropy observed between the 3 subfractions on the Chow diet .