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A more recent version of this article appeared on January 1, 2006

Papers In Press, published online ahead of print October 28, 2005
J. Lipid Res., doi:10.1194/jlr.M500343-JLR200
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Submitted on August 3, 2005
Revised on September 20, 2005
Accepted on October 28, 2005

Apolipoprotein A5: Potential modulator of plasma triglyceride levels in Turks

Ugur Hodoglugil, Sinan Tanyolaç, David W. Williamson, Yadong Huang, and Robert W. Mahley

The J. David Gladstone Institutes, San Francisco, CA 94158

Corresponding Author: srichmond{at}gladstone.ucsf.edu

Apolipoprotein A5 (APOA5) plays an important role in determining plasma triglyceride levels. We studied the effect 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 about 3000 subjects. The rare alleles of the –1464T>C, –1131T>C, S19W, and 1259T>C SNPs were each significantly associated with elevated triglyceride levels (19 to 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 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 a significant elevation in plasma triglyceride levels. At least one of these alleles was present in about 40% of the Turks. Similar associations were observed for –1131T>C and S19W in white Americans living in San Francisco, CA.


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