Published online before print December 26, 2002, doi: 10.1161/01.ATV.0000054194.78240.45
© 2003 American Heart Association, Inc.
ATVB In Focus |
Apolipoprotein A5, a Newly Identified Gene That Affects Plasma Triglyceride Levels in Humans and Mice
From the Genome Sciences Department, Lawrence Berkeley National Laboratory, Berkeley, Calif.
Correspondence to Dr Len A. Pennacchio, Department of Genome Sciences, MS 84-171, One Cyclotron Rd, Lawrence Berkeley National Laboratory, Berkeley, CA 94720. E-mail LAPennacchio{at}lbl.gov
Abstract
Apolipoprotein A5 (APOA5) is a newly described member of the apolipoprotein gene family whose initial discovery arose from comparative sequence analysis of the mammalian APOA1/C3/A4 gene cluster. Functional studies in mice indicated that alteration in the level of APOA5 significantly affected plasma triglyceride concentrations. Mice that overexpressed human APOA5 displayed significantly reduced triglycerides, whereas mice that lacked apoa5 had a large increase in this lipid parameter. Studies in humans have also suggested an important role for APOA5 in determining plasma triglyceride concentrations. In these experiments, polymorphisms in the human gene were found to define several common haplotypes that were associated with significant changes in triglyceride concentrations in multiple populations. Several separate clinical studies have provided consistent and strong support for the effect with 24% of whites, 35% of blacks, and 53% of Hispanics who carry APOA5 haplotypes associated with increased plasma triglyceride levels. In summary, APOA5 represents a newly discovered gene involved in triglyceride metabolism in both humans and mice whose mechanism of action remains to be deciphered.
Key Words: apolipoprotein A5 • triglyceride
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