A survey for 32 nucleotide deletion in the CCR-5 chemokine receptor gene (deltaccr-5) conferring resistance to human immunodeficiency virus type 1 in different ethnic groups and in chimpanzees.

摘要

The 32 nucleotide deletion in the CCR-5 chemokine receptor gene referred to as deltaccr-5 has been shown to confer resistance to HIV-1. Using PCR, 1,105 human subjects and 33 common chimpanzees were genotyped attributing them to one of the three possible genotypes: wild-type homozygote (w/w); deltaccr-5 homozygote (deltaccr-5/deltaccr-5) and deltaccr-5/wild-type heterozygotes (deltaccr-5/w). The ethnic groups investigated included different Middle Eastern nationalities (mainly Arab) and Russians. Carriers of the deltaccr-5 mutation were found among Arabs, Iranians and Russians. The highest frequency of the mutation was seen in Russians (24.4% of the deltaccr-5 heterozygotes, allele frequency-0.1221). Surprisingly, the only deltaccr-5 homozygote identified in our study was an Egyptian. The origin of the deltaccr-5 mutation in the Middle Eastern populations, both Arab and non-Arab, is most probably due to a gene flow from the Europeans. The frequency of the deltaccr-5 mutation in Russians is one of the highest known. It might be one of the factors contributing to a relatively slow pace of increase in the incidence of sexually acquired HIV infection in Russia. None of the chimpanzees tested was positive for deltaccr-5. Interestingly, the DNA sequence of the chimpanzee CCR-5 gene in the region including the site of the deltaccr-5 mutation, and flanking areas, was virtually identical to the homologous human sequence, only two mismatches (silent substitutions) were found.