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

Abstract

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.

Prevalence of Alleles Associated with HIV Resistance in Russia

“…The CCR5D32 allele frequency found in this study was similar to the frequencies previously reported for Russia. It is interesting to note that the closest figures were found previously in Moscow (0.095, x 2 5 0.31, p 5 0.57) (Kazennova et al, 1998), whereas the frequencies for other regions of Russia were higher (range, 0.11-0.13) (Aseev et al, 1997;Slominskii et al, 1997;Voevodin et al, 1998;Yudin et al, 1998). This could be due to higher proportion of FinnoUgrian population, characterized by high frequency of this allele (Pastinen et al, 1998), in the cohorts from those studies.…”

“…At the same time, limited information concerning only the CCR5D32 distribution in several regions of the Russian Federation is currently available (Aseev et al, 1997;Slominskii et al, 1997;Kazennova et al, 1998;Voevodin et al, 1998;Yudin et al, 1998). The aim of this study was (1) to determine the distribution of CCR5D32, CCR5-59029A/G, CCR2-64I, and SDF1-39A alleles among a representative sample of the Moscow population and (2) to estimate the co-occurrence or genotypic independence of those alleles.…”

Distribution OfCCR-5Δ32,CCR2-64I, andSDF-1-3′AAlleles Among Jordanians

“…For example, the reported prevalence of CCR5-D32 is < 1% in Syria and was absent in Lebanon. 5,18,19 In countries such as Bahrain, Iraq, Kuwait, and Saudi Arabia, the prevalence is approximately equivalent with a distribution of CCR5-D32 between 2% and 3%. 5 The results of the current study showed that the frequency of CCR5-D32 in Jordan is 0.6%.…”

Determination of the CCR5∆32 frequency in Emiratis and Tunisians and the screening of the CCR5 gene for novel alleles in Emiratis

“…Low frequencies have been observed among Kuwaitis, Syrians, and Egyptians from Ismailia (1%, b1%, 0.6%, and 0.5%, respectively) (Salem and Batzer, 2007;Voevodin et al, 1998). This allele was expected to be completely absent among Egyptians from the Sinai, Sudanese and Yamanis (Martinson et al, 1997;Salem and Batzer, 2007;Voevodin et al, 1998). These findings might not reflect the real frequency of this deletion among the studied populations due to the small size of samples (b 100).…”

“…Within Middle East region, the frequency was found to be 2.8% among Bahrainis, followed by 2.5%, 2.4%, 2.1%, and 0.6% in Lebanese, Iranians, Saudis, and Jordanians, respectively (Gharagozloo et al, 2005;Karam et al, 2004;Khabour et al, 2013;Martinson et al, 1997;Salem et al, 2009;Stephens et al, 1998). Low frequencies have been observed among Kuwaitis, Syrians, and Egyptians from Ismailia (1%, b1%, 0.6%, and 0.5%, respectively) (Salem and Batzer, 2007;Voevodin et al, 1998). This allele was expected to be completely absent among Egyptians from the Sinai, Sudanese and Yamanis (Martinson et al, 1997;Salem and Batzer, 2007;Voevodin et al, 1998).…”