© 1997 American Heart Association, Inc.
Articles |
Genetic Variation in Factor VII Associated with Variation in Plasma Lipoprotein(a) Concentration
From the Departments of Medicine and Clinical Biochemistry, St. Michael's Hospital and University of Toronto, Ontario (R.A.H., P.W.C.), the Department of Biochemistry, Dalhousie University, Halifax, Nova Scotia (W.C.B.); the School of Nursing, University of Victoria, British Columbia (J.H.B.); and the Department of Biochemistry, University of Toronto, Ontario, Canada (P.W.C.).
Correspondence to Robert A. Hegele, MD, DNA Research Laboratory, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, M5B 1W8, Canada. E-mail: robert.hegele{at}utoronto.ca.
Abstract Cross-sectional and prospective studies have shown
that individuals with high plasma lipoprotein(a) [Lp(a)]
concentrations are at increased risk for coronary heart
disease. Size polymorphism of the apolipoprotein(a) [apo(a)]
glycoprotein accounts for 
35% of the variation in
plasma Lp(a) concentrations. However, there is no convincing evidence
for associations between plasma Lp(a) and common genetic variation
outside APO(a), the gene that encodes apo(a). We tested for
association of common genetic variation of candidate genes in lipid
metabolism and also of F7 with variation of plasma Lp(a)
concentrations in Alberta Hutterites. Variation at codon 353 of
F7 has been associated with variation in the plasma factor
VII activity (FVIIc), with the 353Q allele associated with lower
FVIIc and the 353R allele associated with higher FVIIc. We found
significant associations between variation in plasma concentrations of
Lp(a) and both apo(a) isoform size and F7 codon 353
genotype (both P<.0001). The effects on plasma
Lp(a) concentration of the alleles at codon 353 were additive. The
average effects of the F7 353Q and 353R alleles were,
respectively, to decrease by 1.71 µg/mL and to increase by 0.301
µg/mL plasma Lp(a) concentration from the sample mean. This suggests
that common genomic variation in F7 is associated with
variation in plasma Lp(a) concentration.
Key Words: coagulation • lipids • polygenic traits • small effects • thrombolysis