Genetic mediation of cholesterol metabolism in the baboon (Papio cynocephalus)

Genetic effects on serum cholesterol concentration and measures of cholesterol metabolism were investigated in 83 normocholesterolemic juvenile baboons (Papio cynocephalus), the progeny of 6 sires. Sire effects (P < 0.05) were observed for serum cholesterol concentration, cholesterol turnover rate, cholesterol production rate, and several cholesterol pool parameters derived from a two-pool model. The estimates of heritability (h²) for the half-time of the first (t 1 2A) and second exponentials (t₂¹B) derived from serum [¹⁴C]cholesterol decay curves and the cholesterol turnover rate were 0.67, 0.73 and 0.71, respectively. These heritabilities and those for serum cholesterol concentration (h² = 0.44) and cholesterol production rate (h² = 0.56) indicate these characters are moderately to highly heritable. Serum cholesterol concentration was correlated genetically with cholesterol turnover rate (r_g = -0.56), production rate (r_g = -0.41), t 1 2A (r_g = 0.53), and t 1 2B (r_g = 0.39). Correlations among observed values, or phenotypic correlations, were low. Path analyses revealed that the low phenotypic correlation (r_p = 0.02) between serum cholesterol concentration and cholesterol turnover rate was due to genetic and environmental contributions of similar magnitude but opposite in sign. The low phenotypic correlations of serum cholesterol with cholesterol production rate, t 1 2A, and t 1 2B (r_p = -0.24, 0.23, and 0.19, respectively) were due primarily to the genetic contribution since environmental contributions were near zero. Application of similar genetic and path analytic techniques to human populations should enhance our understanding of the low phenotypic relationships previously observed between serum cholesterol and parameters of cholesterol metabolism.