Effects of diet on genetic regulation of lipoprotein metabolism in baboons

Abstract

Several measures of lipoprotein phenotype are significant predictors of cardiovascular risk. Although such lipoprotein phenotypes are under strong genetic control, it is not clear to what extent they are controlled by the same - and by different - genes and whether these relationships may be altered in different dietary environments. Therefore, we measured six lipoprotein traits (three LDL traits - LDLC and apoB concentrations and LDL size - and three HDL traits - HDLC and apoA1 concentrations and HDL size) on each of three diets differing in level of fat and cholesterol. In bivariate analyses, all but two metabolically related trait pairs were genetically correlated, though none were completely correlated, implying additive genetic effects by both pleiotropic and unique genes. In comparing genetic correlations for the same pair of traits across diet, we detected evidence of diet effects on genetic control of these metabolically related traits; specifically, increasing level of dietary cholesterol was associated with a significant decrease in the genetic correlation of apoA1 with HDL size, and a significant increase in the genetic correlations of LDL size with LDLC and apoB. The results suggest a complex network of genes affecting lipoprotein metabolism: the genes may exert both unique and pleiotropic effects; the genes may exert detectable effects in many or only in specific dietary environments.

Diet‐induced early‐stage atherosclerosis in baboons: Lipoproteins, atherogenesis, and arterial compliance

“…Also, as the concentrations of circulating risk factors like LDLC either peak or plateau at or before seven weeks, the model likely would be valuable for further studies of genetic and environmental (intrinsic and extrinsic) factors that influence variation in the norms of reaction for lipid and cholesterol homeostasis in the continued presence of dietary stressors. Previous studies in the larger pedigreed baboon breeding colony from which these animals were selected have provided evidence for shared (pleiotropic) genetic effects, as well as diet-specific genetic effects on many of these circulating atherosclerosis risk factors in the two dietary environments studied here 58–60 .…”

Identification of genetic drivers of plasma lipoproteins in the Diversity Outbred mouse population

“…In pedigreed baboons, high fat and/or high cholesterol diets increased variance and reduced h 2 in plasma HDL-C, median HDL size, and ApoA1/ApoB protein abundance compared to a low-fat, low-cholesterol diet (62). In a survey of 13 inbred mouse strains fed a Western diet, up to 75% of variance in lean body weight could be attributed to genetics (h 2 ), whereas other phenotypes (e.g., plasma glucose) showed reduced heritability (h 2 < 20%) (63).…”

Identification of genetic drivers of plasma lipoprotein size in the Diversity Outbred mouse population

“…Previous reports have highlighted an interaction between diet and genetics that alters heritability of metabolic phenotypes. In pedigreed baboons, high fat and/or high cholesterol diets increased variance and reduced h 2 in plasma HDL-C, median HDL size, and ApoA1/ApoB protein abundance compared with a low-fat, low-cholesterol diet ( 62 ). In a survey of 13 inbred mouse strains fed a Western diet, up to 75% of variance in lean body weight could be attributed to genetics ( h 2 ), whereas other phenotypes (e.g., plasma glucose) showed reduced heritability ( h 2 < 20%) ( 63 ).…”