title: Multiple genetic determinants of variation of plasma lipoproteins in Alberta Hutterites.
abstract: We hypothesized that variation of nine candidate genes in lipoprotein metabolism would be associated with variation in fasting plasma lipoprotein variables in 718 Alberta Hutterites, a genetic isolate. We measured plasma lipids, lipoproteins, and apolipoproteins and analyzed DNA for genotypes of apolipoprotein (apo) B (APOB), paraoxonase (PON), lipoprotein lipase (LPL), VLDL receptor (VLDLR), apo CIII (APOC3), LDL receptor-related protein (LRP), hepatic lipase (HL), LDL receptor (LDLR), and apo E (APOE). Using a multivariate analysis, we found that (1) genotypes of APOB, PON, LPL, LDLR, and APOE were significantly associated with variation of plasma apo B-related traits; (2) genotypes of PON, LPL, and APOC3 were significantly associated with variation in plasma triglycerides; and (3) genotypes of VLDLR, APOC3, LDLR, and APOE were significantly associated with variation in plasma apo AI and HDL cholesterol. Regression analysis showed that between 3.2% and 7.8% of the total variation in plasma lipoproteins was accounted for by variation in the candidate genes tested. The observations demonstrate a modest but significant genetic component of variation in plasma lipoprotein levels that is due to the candidate genes studied in this normolipemic human genetic isolate.
authors.affiliation: Department of Medicine, St Michael's Hospital, University of Toronto, Ontario, Canada.
authors.forename: R A
authors.initials: RA
authors.lastname: Hegele
authors.forename: J H
authors.initials: JH
authors.lastname: Brunt
authors.forename: P W
authors.initials: PW
authors.lastname: Connelly
mesh_terms: D000416:Alberta; D000483:Alleles; D016632:Apolipoprotein A-I / Q000378:metabolism; D001055:Apolipoproteins B / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D043303:Aryldialkylphosphatase; D008076:Cholesterol, HDL / Q000097:blood; D004950:Esterases / Q000235:genetics; D005006:Ethnicity; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics; D008074:Lipoproteins / Q000097:blood / Q000235:genetics*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D011971:Receptors, Immunologic / Q000235:genetics; D012044:Regression Analysis; D014280:Triglycerides / Q000235:genetics
chemical_list: D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008074:Lipoproteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D014280:Triglycerides; D004950:Esterases; D008071:Lipoprotein Lipase; D043303:Aryldialkylphosphatase