J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M500343-JLR200 on October 28, 2005

Papers In Press, published online ahead of print January 1, 2006
J. Lipid Res., doi:10.1194/jlr.M500343-JLR200
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Journal of Lipid Research, Vol. 47, 144-153, January 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Apolipoprotein A-V: a potential modulator of plasma triglyceride levels in Turksboxs

Ugur Hodoglugil*,{dagger}, Sinan Tanyolaç*,§, David W. Williamson*,**, Yadong Huang*,{dagger}{dagger} and Robert W. Mahley1,*,{dagger},{dagger}{dagger},§§

* Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, San Francisco, CA
{dagger} Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA
** Graduate Program in Biological and Medical Informatics, University of California, San Francisco, San Francisco, CA
{dagger}{dagger} Department of Pathology, University of California, San Francisco, San Francisco, CA
§§ Department of Medicine, University of California, San Francisco, San Francisco, CA
§ Faculty of Medicine, Department of Internal Medicine, Division of Endocrinology and Metabolism, Istanbul University, Istanbul, Turkey

boxs The online version of this article (available at http://www.jlr.org) contains three additional tables.

Published, JLR Papers in Press, October 28, 2005.

1 To whom correspondence should be addressed. e-mail: rmahley{at}gladstone.ucsf.edu

The apolipoprotein A-V gene (APOA5) plays an important role in determining plasma triglyceride levels. We studied the effects of APOA5 polymorphisms on plasma triglyceride levels in Turks, a population with low levels of HDL cholesterol and a high prevalence of coronary artery disease. We found 15 polymorphisms, three of which were novel. Seven haplotype-tagging single nucleotide polymorphisms (SNPs) were chosen and genotyped in ~3,000 subjects. The rare alleles of the –1464T>C, –1131T>C, S19W, and 1259T>C SNPs were significantly associated with increased triglyceride levels (19–86 mg/dl; P < 0.05) and had clear gene-dose effects. Haplotype analysis of the nine common APOA5 haplotypes revealed significant effects on triglyceride levels (P < 0.001). Detailed analysis of haplotypes clearly showed that the –1464T>C polymorphism had no effect by itself but was a marker for the –1131T>C, S19W, and 1259T>C polymorphisms. The –1131T>C and 1259T>C polymorphisms were in a strong but incomplete linkage disequilibrium and appeared to have independent effects. Thus, the APOA5 –1131T>C, S19W, and 1259T>C rare alleles were associated with significant increases in plasma triglyceride levels. At least one of these alleles was present in ~40% of the Turks. Similar associations were observed for –1131T>C and S19W in white Americans living in San Francisco, California.

Supplementary key words Turkish population • polymorphism • haplotype • high density lipoprotein cholesterol

Abbreviations: APOA5, apolipoprotein A-V gene; BMI, body mass index; CAD, coronary artery disease; HDL-C, high density lipoprotein cholesterol; htSNP, haplotype-tagging single nucleotide polymorphism; LD, linkage disequilibrium; SNP, single nucleotide polymorphism; THS, Turkish Heart Study; UTR, untranslated region


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