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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2753-2758.)
© 1997 American Heart Association, Inc.

Articles

Common Genomic Variation in the APOC3 Promoter Associated With Variation in Plasma Lipoproteins

Robert A. Hegele; Philip W. Connelly; Anthony J. G. Hanley; Fang Sun; Stewart B. Harris; ; Bernard Zinman

From the Department of Medicine, St Michael's Hospital (R.A.H., P.W.C., F.S.), and Samuel Lunenfeld Research Institute and Mount Sinai Hospital (A.J.G.H., B.Z.), University of Toronto; and Thames Valley Family Practice Research Unit, University of Western Ontario, London (S.B.H.), Canada.

Correspondence to Robert A. Hegele, MD, The Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, Room 406-100, Perth Dr, London, Toronto, Ontario, Canada N6A 5K8. E-mail robert.hegele{at}rri.on.ca

Abstract We hypothesized that common genomic variation that affected the expression and/or function of the products of the APOC3, APOE, FABP2, and PON1 genes would be associated with variation in biochemical phenotypes in a previously unstudied human sample. We determined genotypes of functional genomic variants of APOC3, APOE, FABP2, and PON1 in 509 adult aboriginal Canadians from an isolated community in Northern Ontario. We tested for genotype associations with plasma lipoprotein traits. We found that (1) common variation at nucleotide -455 of the APOC3 promoter was associated with variation in plasma triglycerides (P=.006) and (2) common variation of APOE determining plasma isoforms of apo E was associated with variation in plasma apo B (P=.009). Analysis of subjects classed by APOC3 markers showed that homozygosity for presence of a C at nucleotide -455 and a T at nucleotide -482 was associated with significantly increased plasma triglycerides in both men and women. Furthermore, this allele was approximately twice as frequent in subjects within the highest quartile of plasma triglycerides as in subjects within the lowest quartile. Since the DNA variation detected by the APOC3 markers affects in vitro expression of the gene product, it is possible that the marker itself caused the associations. However, the associations could also have resulted from linkage disequilibrium with other functional variants in APOC3 or the closely linked APOA1 and/or APOA4 genes.

Key Words: insulin-response element • hyperlipidemia • gene promoter • linkage disequilibrium • polygenic traits

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