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An Apolipoprotein Influencing Triglycerides in Humans and Mice Revealed by Comparative Sequencing

Science  05 Oct 2001:
Vol. 294, Issue 5540, pp. 169-173
DOI: 10.1126/science.1064852

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Abstract

Comparison of genomic DNA sequences from human and mouse revealed a new apolipoprotein (APO) gene (APOAV) located proximal to the well-characterized APOAI/CIII/AIV gene cluster on human 11q23. Mice expressing a human APOAVtransgene showed a decrease in plasma triglyceride concentrations to one-third of those in control mice; conversely, knockout mice lackingApoav had four times as much plasma triglycerides as controls. In humans, single nucleotide polymorphisms (SNPs) across theAPOAV locus were found to be significantly associated with plasma triglyceride levels in two independent studies. These findings indicate that APOAV is an important determinant of plasma triglyceride levels, a major risk factor for coronary artery disease.

  • * Present address: Human and Molecular Genetics Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.

  • To whom correspondence should be addressed. E-mail: EMRubin{at}lbl.gov

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