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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:861-871.)
© 1995 American Heart Association, Inc.

Articles

Multiple Genetic Determinants of Variation of Plasma Lipoproteins in Alberta Hutterites

Robert A. Hegele; J. Howard Brunt; Philip W. Connelly

From the Departments of Medicine, Clinical Biochemistry (R.A.H., P.W.C.), and Biochemistry (P.W.C.), St Michael's Hospital, University of Toronto, Ontario, and School of Nursing, University of Victoria, British Columbia (J.H.B.), Canada.

Correspondence to Robert A. Hegele, MD, DNA Research Laboratory, St Michael's Hospital, 30 Bond St, Toronto, Ontario, Canada M5B 1W8. E-mail robert.hegele@utoronto.ca.

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.

Key Words: genetic association study • DNA markers • polygenic traits

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