Lawrence Berkeley National Laboratory

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 impacted plasma triglyceride concentrations. Mice over-expressing human APOA5 displayed significantly reduced triglycerides, while mice lacking 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 percent of Caucasians, 35 percent of African-Americans and 53 percent of Hispanics carrying 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.