Multiple genetic determinants of variation of plasma lipoproteins in Alberta Hutterites.
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.
Hegele
R A
RA
Department of Medicine, St Michael's Hospital, University of Toronto, Ontario, Canada.
Brunt
J H
JH
Connelly
P W
PW
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
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