title: Investigation of LRP8 gene in 1p31 QTL linked to LDL peak particle diameter in the Quebec family study.
abstract: The small, dense LDL phenotype is associated with an increased cardiovascular disease risk. A genome-wide scan performed on 236 nuclear families of the Quebec Family Study (QFS) revealed a quantitative trait locus affecting LDL peak particle diameter (LDL-PPD) and density on the 1p31 region. This region contains the low-density lipoprotein receptor-related protein 8 (LRP8) gene. LRP8, a receptor for apolipoprotein (apo) E, modulates apoE levels, thus contributing to plasma cholesterol and triglyceride (TG) concentrations. We investigate the effects of LRP8 polymorphisms on LDL-PPD, on the relative proportion of small LDL (<255Å) and the absolute concentration of cholesterol among the small LDL particles. LRP8 rs5174 was associated with LDL-PPD and estimated cholesterol concentrations in the small LDL particles adjusted for the effects of age and sex (p=0.008, p=0.04, respectively). LRP8 rs3820198 was associated with total and LDL-cholesterol levels as well as with apoB concentrations adjusted for the effects of age and sex (p=0.005, p=0.004 and p=0.01, respectively) but not with LDL size-related variables. These results suggest that LRP8 gene polymorphisms influence plasma cholesterol levels as well as size and composition of LDL particles.
authors.affiliation: Department of Food Science and Nutrition, Laval University, Quebec City, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Dolley
authors.forename: B
authors.initials: B
authors.lastname: Lamarche
authors.forename: J P
authors.initials: JP
authors.lastname: Després
authors.forename: C
authors.initials: C
authors.lastname: Bouchard
authors.forename: L
authors.initials: L
authors.lastname: Pérusse
authors.forename: M C
authors.initials: MC
authors.lastname: Vohl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood / Q000737:chemistry*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D015810:Linkage Disequilibrium; D050356:Lipid Metabolism / Q000235:genetics; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010316:Particle Size; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D026502:LDL-Receptor Related Proteins; D008075:Lipoproteins, HDL; D014280:Triglycerides; C098773:low density lipoprotein receptor-related protein 8