A major gene influences variation in large HDL particles and their response to diet in baboons

Abstract

Some baboons accumulate appreciable amounts of large apoE-rich HDLs (HDL 1) which are similar to those reported in humans with several different dyslipoproteinemias. We estimated HDL 1 cholesterol concentrations by gradient gel electrophoresis of serum samples obtained from 634 pedigreed baboons fed with three diets differing in levels of fat and cholesterol. The HDL 1 trait was highly heritable on each diet (0.390≤ h 2≤0.528). Segregation analyses yielded significant evidence that a single major gene plus polygenes affected HDL 1 on a high-fat low-cholesterol diet. The major gene explained approximately 56% of total trait variance and 90% of the additive genetic variance in HDL 1 levels in these baboons. Bivariate one-locus segregation analyses indicated that this major gene exerts significant pleiotropic effects on a number of traditional HDL traits on all three diets, including HDL size distributions, and concentrations of HDL-C, apoAI, and apoE. Linkage analyses showed that this major gene was not located in chromosomal regions that contain six candidate genes whose protein products are important to HDL metabolism ( LCAT, CETP, APOA1, APOE, ABCA1, LIPC). Our results suggest this major gene in baboons plays a pivotal role in HDL metabolism, but is unlikely to code for any of the proteins previously implicated in studies of human HDL 1.