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Cited by 26Lipid metabolism and disordersGenetic Associations and EpidemiologyLipoproteins and Cardiovascular Health

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In vivo characterization of human APOA5 haplotypes

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Ahituv, Nadav, Akiyama, Jennifer, Chapman-Helleboid, Audrey, Fruchart, Jamila, Pennacchio, Len A.·2007·Genomics
DOI 10.1016/j.ygeno.2007.08.003
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Abstract

Increased plasma triglyceride concentrations are an independent risk factor for cardiovascular disease. Numerous studies support a reproducible genetic association between two minor haplotypes in the human apolipoprotein A5 gene (APOA5) and increased plasma triglyceride concentrations. We thus sought to investigate the effects of these minor haplotypes (APOA5*2 and APOA5*3) on ApoAV plasma levels through the precise insertion of single-copy APOA5 haplotypes at a targeted location (Hprt) in the mouse genome. While we found no difference in the amount of human plasma ApoAV in mice containing the common APOA5*1 or minor APOA5*2 haplotype, the introduction of the single APOA5*3-defining allele (19W) resulted in three fold lower ApoAV plasma levels, consistent with existing genetic association studies. These results indicate that the S19W polymorphism is likely to be functional and explain the strong association of this variant with plasma triglycerides, supporting the value of sensitive in vivo assays to define the functional nature of human haplotypes.

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  • The minor allele of rs3135506 (minor allele frequency about 6% in whites) has been repeatedly associated with increased plasma triglyceride concentrations.

    “The minor allele of rs3135506 (minor allele frequency (MAF) of about 6% in whites) has been repeatedly associated with increased plasma TG concentrations [96–99].”

    From Fenofibrate and metabolic syndrome (2010) · cites this paper as [96]

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Metadata

Authors
Ahituv, N., Akiyama, J., Chapman-Helleboid, A., Fruchart, J., & Pennacchio, L. A.
Affiliations
  • Lawrence Berkeley National Laboratory (US)
  • Inserm (FR)
Corresponding author
Pennacchio, Len A.
ORCID
Venue
Genomics
Publisher
Elsevier BV
Published
2007-12
Volume
90
Issue
6
Pages
674-679
ISSN
0888-7543 (ISSN-L)
DOI
10.1016/j.ygeno.2007.08.003
OpenAlex
W110103096
Cited by
26
References
33
Citations by year
2026: 1 · 2020: 1 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 3
FWCI
3.76
Type
journal article
Language
en
Open access
Licence
Locations
  • Genomics (publishedVersion)
  • PubMed (publishedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
  • University of North Texas Digital Library (University of North Texas) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • Lawrence Berkeley National Laboratory
Funders
  • U.S. Department of Energy (-AC02-05CH11231, 05CH11231, DE-AC02-)
  • National Heart, Lung, and Blood Institute (HL071954, R01HL071954)
  • Lawrence Berkeley National Laboratory (AC02‐05CH11231, DE-AC02-05CH11231, 05CH11231)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Keywords
APOA5, plasma triglycerides, genetic association, cardiovascular risk, transgenic mouse model, functional polymorphisms
MeSH terms
Apolipoprotein A-V, Animals, Apolipoproteins A, Base Sequence, Haplotypes, Humans, Hypoxanthine Phosphoribosyltransferase, Male, Mice, Inbred C57BL, Mice, Transgenic, Recombinant Proteins, Triglycerides, Genetic Variation, Mutagenesis, Site-Directed, DNA Primers, Polymorphism, Single Nucleotide, Mice

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