Localization of genes that control LDL size fractions in baboons.

LDL phenotypes are strongly associated with risk of cardiovascular disease and are heritable, although little is known about individual genes that influence them. We investigated genetic control of LDL size-related phenotypes in 634 pedigreed baboons fed three diets contrasting in levels of fat and cholesterol. On a high-cholesterol high-fat diet, we obtained significant evidence for a quantitative trait locus (QTL) for cholesterol concentrations of lipoproteins between 27 and 28 nm (LOD=4.22, genomic P=0.0047) on the baboon homologue of human chromosome 22. For baboons fed a low-cholesterol high-fat diet, we obtained suggestive evidence for a QTL for cholesterol concentrations between 26 and 27 nm (LOD=2.67) on the baboon homologue of human chromosome 5. We speculate that this QTL influences LDL size distributions because LDL median diameters and other LDL fractions also showed peak LOD scores in this same chromosomal region. On a low-cholesterol low-fat basal diet we obtained suggestive evidence for a QTL for cholesterol concentrations of lipoproteins between 26 and 27 nm in diameter (LOD=2.15) on the baboon homologue of human chromosome 16. Thus, we have evidence for three putative QTLs that influence variation in baboon LDL size phenotypes on different diets.