Quantitative Trait Loci Influencing Blood and Liver Cholesterol Concentration in Rats

OBJECTIVE—The LEW/OlaHsd and BC/CpbU rat inbred strains differ markedly in blood and hepatic cholesterol levels before and after a cholesterol-rich diet. To define loci controlling these traits and related phenotypes, an F2 population derived from these strains was genetically analyzed. METHODS AND RESULTS—For each of the 192 F2 animals, phenotypes were determined, and genomic DNA was screened for polymorphic microsatellite markers. Significant quantitative trait loci (QTLs) were detected for basal serum cholesterol level on chromosome 1 (D1Rat335-D1Rat27total population, lod score 9.6; females, lod score 10.3) and chromosome 7 (D7Rat69males, lod score 4.1), for postdietary serum cholesterol level on chromosome 2 (D2Rat69total population, lod score 4.4) and chromosome 16 (D16Rat6-D16Rat44total population, lod score 3.3), for postdietary serum phospholipid level on chromosome 11 (D11Rat10total population, lod score 4.1; females, lod score 3.6), and for postdietary serum aldosterone level on chromosome 1 (D1Rat14females, lod score 3.7) and chromosome 18 (D18Rat55-D18Rat8females, lod score 2.9). In addition, QTLs with borderline significance were found on chromosomes 3, 5 to 11, 15, and 18. CONCLUSIONS—QTLs involved in blood and/or hepatic cholesterol concentrations (or related phenotypes) in the rat were identified. This contributes to the value of the rat as an animal model in studies researching the role of cholesterol in the pathogenesis of atherosclerosis and other cholesterol-related diseases.