APOLIPOPROTEIN-E IN HYPERLIPIDEMIA

Purpose: To review DNA analysis of apolipoprotein E used to assess pat ients with hyperlipidemia. Data Sources and Study Selection: 44 basic science studies of molecular analysis; 42 basic science studies of the biochemical, cellular biological, and molecular biological features o f apolipoprotein E; and 29 clinical investigational studies, meta-anal yses, and case series of patients with mutations in apolipoprotein E. Data Extraction: Methods of DNA analysis were reviewed, using specific examples in human disease, and the role of apolipoprotein E in normal and disordered lipoprotein metabolism was reviewed. Genetic analysis of apolipoprotein E in populations and particularly in persons with ty pe III hyperlipoproteinemia is reviewed. Data Synthesis: In the genera l population, common DNA variants of apolipoprotein E are consistently associated with modest differences in plasma lipids and lipoproteins. Homozygosity for the E2 isoform of apolipoprotein E predisposes some patients to the development of type III hyperlipoproteinemia, a condit ion that involves an additional genetic or environmental factor for fu ll clinical expression. Rare mutations of apolipoprotein E also cause hyperlipidemia. Conclusions: DNA variation of apolipoprotein E is one of several genetic and environmental factors that interact in a comple x manner to affect plasma lipoproteins. DNA analysis of apolipoprotein E can be used in persons with hyperlipidemia to identify those with t ype III hyperlipoproteinemia and in relatives of affected persons to i dentify those who are predisposed.