Apolipoprotein E (APOE) allele distribution in the world. Is APOE*4 a 'thrifty' allele?

Apolipoprotein E (APOE = gene, apoE = protein) plays a central role in plas ma lipoprotein metabolism and in lipid transport within tissues. The APOE s hows a genetic polymorphism determined by three common alleles, APOE*2, APO E*3, APOE*4 and the product of the three alleles differs in several functio nal properties. APOE is involved in the development of certain pathological conditions. In particular, the APOE*4 allele is a risk factor for suscepti bility to coronary artery disease (CAD) and Alzheimer's Disease (AD). In th e present study we analyzed the APOE allele distribution in the world. The APOE*3 is the most frequent in all the human groups, especially in populati ons with a long-established agricultural economy like those of the Mediterr anean basin (0.849-0.898). The frequency of APOE*4, the ancestral allele, r emains higher in populations like Pygmies (0.407) and Khoi San (0.370), abo rigines of Malaysia (0.240) and Australia (0.260), Papuans (0.368), some Na tive Americans (0.280), and Lapps (0.310) where an economy of foraging stil l exists, or food supply is (or was until the recent past) scarce and spora dically available. The APOE*2 frequency fluctuates with no apparent trend ( 0.145-0.02) and is absent in Native Americans. We suggest that the APOE*4, based on some functional properties it has and on its distribution among hu man populations, could be identified as a 'thrifty' allele. The exposure of APOE*4 to the contemporary environmental conditions (Western diet, longer lifespans) could have rendered it a susceptibility allele for CAD and AD. T he absence of the association of APOE*4 with CAD and AD in Sub-Saharan Afri cans, and its presence in African Americans, seems to confirm this hypothes is.