In Vivo Characterization of Human APOA5 Haplotypes

Journal Article · Sun Oct 01 04:00:00 EDT 2006 · Genomics

OSTI ID:928488

Ahituv, Nadav; Akiyama, Jennifer; Chapman-Helleboid, Audrey; Fruchart, Jamila; Pennacchio, Len A

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.

• Research Organization: Ernest Orlando Lawrence Berkeley NationalLaboratory, Berkeley, CA (US)
• Sponsoring Organization: USDOE Director, Office of Science; National Institutes ofHealth
• DOE Contract Number: AC02-05CH11231
• OSTI ID: 928488
• Report Number(s): LBNL--61860; BnR: 400412000
• Journal Information: Genomics, Journal Name: Genomics Journal Issue: 6 Vol. 90; ISSN GNMCEP; ISSN 0888-7543
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOLIPOPROTEINS
CARDIOVASCULAR DISEASES
FUNCTIONALS
GENES
GENETICS
IN VIVO
MICE
PLASMA
TRIGLYCERIDES