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

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-thir...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2001-10, Vol.294 (5540), p.169-173
Main Authors: Pennacchio, Len A., Olivier, Michael, Hubacek, Jaroslav A., Cohen, Jonathan C., Cox, David R., Fruchart, Jean-Charles, Krauss, Ronald M., Rubin, Edward M.
Format: Article
Language:English
Subjects:
Adult
Alleles
Analysis
Animals
APOAV gene
Apolipoprotein A-V
Apolipoprotein C-III
Apolipoproteins
Apolipoproteins - genetics
Apolipoproteins - physiology
Apolipoproteins A
Apolipoproteins C - blood
Biochemistry
Biological and medical sciences
Cardiovascular diseases
chromosome 11
Chromosomes, Human, Pair 11
Cohort Studies
Computational Biology
coronary artery disease
Coronary Disease - etiology
Coronary Disease - genetics
Coronary vessels
Deoxyribonucleic acid
DNA
Expressed Sequence Tags
Female
Fractions
Fundamental and applied biological sciences. Psychology
Genes
Genomics
Genotypes
Haplotypes
Human genetics
Humans
Independent Study
Linkage Disequilibrium
Lipids
Lipoproteins, VLDL - blood
Liver
Male
Mice
Mice, Knockout
Mice, Transgenic
Molecular and cellular biology
Multigene Family
Open Reading Frames
Polymerase chain reaction
Polymorphism, Single Nucleotide
Proteins
Risk Factors
RNA
Sequence Analysis, DNA
Studies
Transcripts (Written Records)
Transgenes
Transgenic animals
Triglycerides
Triglycerides - blood
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Description
Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1064852