Quantitative Trait Loci Influencing Blood and Liver Cholesterol Concentration in Rats

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 22; no. 12; pp. 2072 - 2079
• Main Authors: Bonné, Anita C.M, den Bieman, Maria G, Gillissen, Gert F, Lankhorst, Ægidius, Kenyon, Christopher J, van Zutphen, Bert F.M, van Lith, Hein A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.12.2002; Hagerstown, MD Lippincott
• Subjects: Animals; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cholesterol - blood; Cholesterol - genetics; Cholesterol - metabolism; Cholesterol - physiology; Cholesterol, Dietary - metabolism; Chromosome Mapping - methods; Diet; Disease Models, Animal; Female; Gene Expression Regulation - genetics; Genes - genetics; Liver - chemistry; Male; Medical sciences; Microsatellite Repeats - genetics; Phenotype; Phospholipids - blood; Polymorphism, Genetic - genetics; Quantitative Trait Loci - genetics; Rats; Rats, Inbred Lew; Rats, Inbred Strains; Rat; Pathogenesis; Liver; Rodentia; Cardiovascular disease; Lipids; phospholipids; Genetic determinism; Cholesterol; Blood plasma; Vascular disease; Quantitative trait loci; Vertebrata; Mammalia; Animal; Atherosclerosis; Risk factor; rats; steroid hormones
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.ATV.0000040225.16592.CE

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.