Apolipoprotein E Polymorphisms and Concentration in Chronic Diseases and Drug Responses

Abstract

Apolipoprotein (apo) E is an important circulating and tissue protein involved in cholesterol homeostasis and many other functions. The common polymorphism in the coding region of the gene, four polymorphisms in the promoter region, other additional single nucleotide polymorphisms, as well as several apo E variants have been identified. The common coding polymorphism strongly influences the lipid metabolism and the circulating concentration of apo 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 therapy, 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 concentration appears to be altered in diseases and can be modulated by some of the drugs cited above. This parameter can thus also give interesting clinical information and could be a therapeutic target, providing it is validated. At the present time, we cannot exclude that apo E concentration may be the most prominent apo E parameter to be considered in health and disease, while apo E polymorphisms would represent only secondary parameters influencing apo E concentration.

Association of Estrogen Receptor α (ESR1) <i>Pvu</i>II and <i>Xba</i>I Polymorphisms with Sporadic Alzheimer’s Disease and Their Effect on Apolipoprotein E Concentrations

“…Because apoE levels are reduced in both the plasma [21] and the cerebrospinal fl uid [22] of AD patients, and, similarly, the lowest apoE levels are associated with e*4/e*4 homozygotes in both the plasma [23] and the brain [24] , we can assume that the data on plasma apoE are indicative of brain apoE behavior as well.…”

Apolipoprotein E polymorphism is associated with age of onset in schizophrenia

“…It is expressed in humans as three common isoforms coded by three different alleles, APOE e2, e3, and e4, resulting in six genotypes (e2/2, e2/3, e2/4, e3/3, e3/4, and e4/4) (Siest et al 2000). The APOE isoforms are characterized by the presence of amino acid Cys (APOE 2 and APOE 3) or Arg (APOE 4) at position 112 of the mature APOE polypeptide chain and Arg (APOE 3 and APOE 4) or Cys (APOE 2) at position 158 (Weisgraber et al 1981).…”

The importance of plasma apolipoprotein E concentration in addition to its common polymorphism on inter-individual variation in lipid levels: results from Apo Europe

“…This polymorphism results in six genotypes, three heterozygote e3/e2, e3/e4, e4/e2 and three homozygote genotypes e2/e2, e3/e3 and e4/e4. 2 The alleles encode isoforms of apoE, which differ in terms of their interaction with cell surface receptors, and catabolism of apoB-containing lipoproteins.…”

“…The specific objectives are: (1) to determine the factors affecting interindividual variation in apoE plasma concentration, particularly the role of apoE genetic polymorphism; (2) To study the distribution of apoE genotype/apoE plasma concentration across different European populations; (3) To evaluate , in case-control studies, the role of apoE plasma concentration together with apoE genotype as risk factors for: coronary artery disease and alzheimer disease. More details on ApoEurope project are given by Schiele et al 7 Our study presents a useful element for going deeper in the different steps of the ApoEurope project by investigating the combined usefulness of the apoE genotype and concentration.…”