Apolipoprotein E polymorphisms and concentration in chronic diseases and drug responses

Apolipoprotein (apo) E is an important circulating and tissue protein invol ved in cholesterol homeostasis and many other functions. The common polymor phism in the coding region of the gene, four polymorphisms in the promoter region, other additional single nucleotide polymorphisms, as well as severa l apo E variants have been identified. The common coding polymorphism stron gly influences the lipid metabolism and the circulating concentration of ap o E itself. This polymorphism is at the origin of the implication of apo E in cardiovascular and neurodegenerative diseases, but also of the relation of apo E with longevity. Probably due to its many metabolic and functional consequences, apo E polymorphism has been shown to influence the responses of patients to several drugs (fibrates, statins, hormone replacement therap y, anti-Alzheimer drugs) or environmental interventions (black tea, alcohol , diet). Apo E genotyping may be clinically helpful in defining the risk of patients and their responses to therapeutics. Finally, circulating apo E c oncentration appears to be altered in diseases and can be modulated by some of the drugs cited above. This parameter can thus also give interesting cl inical information and could be a therapeutic target, providing it is valid ated. At the present time, we cannot exclude that apo E concentration may b e the most prominent apo E parameter to be considered in health and disease , while apo E polymorphisms would represent only secondary parameters influ encing apo E concentration.