Haplotype analysis of the apolipoprotein E and apolipoprotein C1 loci in Portugal and Sao Tome e Principe (Gulf of Guinea): Linkage disequilibrium evidence that APOE*4 is the ancestral APOE allele

The joint distributions of phenotypes from the apolipoprotein E gene (APOE) and from a closely linked restriction site polymorphism at the apolipoprot ein C1 locus (APOC1) were studied in population samples from Portugal and S ao Tome e Principe (Gulf of Guinea), a former Portuguese colony that was or iginally populated by slaves imported from the African mainland. The freque ncies of the APOE alleles (*2, *3, and *4) in Portugal and Sao Tome fitted the ranges of variation generally observed in European and African populati ons, respectively. Haplotype analysis showed that in both populations the s trength of linkage disequilibrium was highest for the APOE*2 allele and low est for the APOE*4 allele, suggesting that the origin of the APOE alleles f ollowed a 4 --> 3 --> 2 pathway and thus providing independent confirmation of the results from sequence homology studies with nonhuman primates. In a ccordance with global trends in the distribution of human genetic variation , the European sample from Portugal presented more intense linkage disequil ibrium between APOE and APOC1 than the African sample from Sao Tome where, despite the short 4-kb distance that separates the 2 loci, the level of ass ociation between the APOC1 alleles and APOE*4 was nonsignificant.