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Journal of Lipid Research, Vol. 44, 1167-1173, June 2003
Copyright © 2003 by Lipid Research, Inc.
Genetic analysis of a polymorphism in the human apoA-V gene
: effect on plasma lipids
* Department of Physiological Nursing, University of California San Francisco, San Francisco, CA 94143
Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94143
Department of Medicine, University of California San Francisco, San Francisco, CA 94143
1 To whom correspondence should be addressed. e-mail: bradley.aouizerat{at}nursing.ucsf.edu
Recent discovery and characterization of APOAV suggests a role in metabolism of triglyceride (TG)-rich lipoproteins. Previously, variation at the APOAV locus was shown to modestly influence plasma TGs in normolipidemic samples. The aims of this study were to assess the effects of a polymorphism in APOAV (T-1131C) in terms of its frequency among three dyslipidemic populations and a control population, differences of allele frequency across available ethnic groups, and associations with specific lipoprotein TG and cholesterol compartments. We found a striking elevation in the frequency of the rare allele in a Chinese population (P = 0.0002) compared with Hispanic and European populations. The rare allele of the polymorphism was associated with elevated plasma TG (P = 0.012), VLDL cholesterol (P = 0.0007), and VLDL TG (P = 0.012), LDL TG (P = 0.003), and HDL TG (P = 0.016). Linear regression models predict that possession of the rare allele elevates plasma TG by 21 mg/dl (P = 0.009) and VLDL cholesterol by 8 mg/dl (P = 0.0001), and reduces HDL cholesterol by 2 mg/dl (P = 0.017). The association of the polymorphism with altered lipoprotein profiles was observed in combined hyperlipidemia, hypoalphalipoproteinemia, and hyperalphalipoproteinemia, and in controls.
These findings indicate that APOAV is an important determinant of plasma TG and lipoprotein cholesterol, and is potentially a risk factor for cardiovascular disease.
Supplementary key words lipoprotein • dyslipidemia • ethnicity
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