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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:89-95.)
© 1995 American Heart Association, Inc.

Articles

A Polymorphism of the Paraoxonase Gene Associated With Variation in Plasma Lipoproteins in a Genetic Isolate

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

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

Correspondence to Robert A. Hegele, MD, DNA Research Laboratory, St Michael's Hospital, 30 Bond St, Toronto, Ontario, Canada M5B 1W8.

Abstract The Hutterite Brethren are a genetic isolate characterized by high indices of relatedness and a communal agrarian lifestyle. We hypothesized that variation of the paraoxonase (PON) gene that underlies the interindividual variation in plasma PON activity would be associated with variation in fasting plasma lipoprotein variables in this group. In 793 Hutterites, we measured plasma lipids, lipoproteins, and apolipoproteins and analyzed DNA for genotypes of the protein polymorphism at amino acid residue 192 of PON. We observed that genotypes of PON were significantly associated with variation in plasma concentrations of total, HDL, non-HDL, and LDL cholesterol, total triglycerides, and apolipoprotein (apo) B. Homozygotes for the low-activity variant of PON had significantly lower levels of plasma apoB-related biochemical variables than heterozygotes and homozygotes for the high-activity variant of PON. Homozygotes for the low-activity variant of PON also had significantly lower ratios of total cholesterol/HDL cholesterol, LDL cholesterol/HDL cholesterol, and apoB/apoA-I than heterozygotes and homozygotes for the high-activity variant of PON. We found no evidence for a gene-gender interaction for any plasma lipoprotein variable. The PON polymorphism accounted for about 1% of the variation in total cholesterol and related lipoprotein traits in the Hutterites. These observations suggest that PON is a significant genetic determinant of plasma lipoprotein levels.

Key Words: association study • DNA • lipids • oxidation • polygenic traits

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