In Vivo Characterization of Human APOA5 Haplotypes [electronic resource].
- Washington, D.C. : United States. Dept. of Energy, 2006. and Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy.
- Additional Creators:
- United States. Department of Energy, National Institutes of Health (U.S.), and United States. Department of Energy. Office of Scientific and Technical Information
- Increased plasma triglycerides 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 effect of these minor haplotypes (APOA5*2 and APOA5*3) on ApoAV plasma levels through the precise insertion of single-copy intact APOA5 haplotypes at a targeted location in the mouse genome. While we found no difference in the amount of human plasma ApoAV in mice containing the common APOA5*1 and minor APOA5*2 haplotype, the introduction of the single APOA5*3 defining allele (19W) resulted in 3-fold lower ApoAV plasma levels consistent with existing genetic association studies. These results indicate that 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.
- Published through SciTech Connect., 10/01/2006., "lbnl--61860", ": 400412000", Genomics 90 6 ISSN 0888-7543; GNMCEP FT, Pennacchio, Len A.; Akiyama, Jennifer; Fruchart, Jamila; Ahituv, Nadav; Chapman-Helleboid, Audrey., and Ernest Orlando Lawrence Berkeley NationalLaboratory, Berkeley, CA (US)
- Funding Information:
- DE-AC02-05CH11231, NIH:RHL071954A, and GHRUB4
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