An Apolipoprotein Influencing Triglycerides in Humans and Mice Revealed by Comparative Sequencing-Reference-Cited by-同舟云学术

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

Published:2001-10-05 Issue:5540 Volume:294 Page:169-173
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Pennacchio Len A.¹,Olivier Michael²,Hubacek Jaroslav A.³,Cohen Jonathan C.³,Cox David R.²,Fruchart Jean-Charles⁴,Krauss Ronald M.¹,Rubin Edward M.¹

Affiliation:

1. Genome Sciences Department, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.

2. Stanford Human Genome Center, Department of Genetics, Stanford University School of Medicine, 975 California Avenue, Palo Alto, CA 94304, USA.

3. Center for Human Nutrition and McDermott, Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390–9052, USA.

4. Department of Atherosclerosis–INSERM U545, Institut Pasteur de Lille, 1, rue du Professeur Calmette, 59019 Lille cedex, France and Faculté de Pharmacie, University of Lille, 59006 Lille cedex, France.

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 APOAV transgene showed a decrease in plasma triglyceride concentrations to one-third of those in control mice; conversely, knockout mice lacking Apoav had four times as much plasma triglycerides as controls. In humans, single nucleotide polymorphisms (SNPs) across the APOAV 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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