Frequency of the CCR5∆32 allele in Brazilians: a study in colorectal cancer and in HTLV-I infection

The cc-chemokine receptor-5 gene protein (CCR5) is a seven-transmembrane-domain G protein coupled receptor that has as its natural ligands RANTES (regulated on activation normal T-cell expressed and secreted), MIP-alpha (macrophage inflammatory protein) and MIP-beta, which are members of the CC subfamily of chemokines (Samson et al., 1996a). The CCR5 protein, in concert with CD4, is also the receptor that mediates the internalization of HIV in macrophages and monocytes (Dragic et al., 1996). Studies of individuals who have been multiply exposed to HIV and yet remain uninfected led to the identification of the CCR5∆32 allele, that exhibits a 32-bp deletion in the CCR5 gene (Liu et al., 1996). Because of a frameshift at amino acid 185 the deleted allele codes for a truncated protein that is consequently not integrated into the cell membrane (Liu et al., 1996). The homozygous state for the CCR5∆32 allele has been shown to be associated with a high degree of protection against HIV infection in vivo (Dean et al., 1996; Huang et al., 1996; Samson et al., 1996b). This protection is not absolute as demonstrated by identification of one HIV-1-infected CCR5∆32 homozygote (Biti et al., 1997; O’Brien et al., 1997). Although there is no evidence for a strong protective effect in heterozygotes (Dean et al., 1996; Huang et al., 1996; Michael et al., 1997), a modest reduction in HIV incidence has been reported (Samson et al., 1996b). Also, the observation that cohorts of long-term survivors are enriched for CCR5∆32 heterozygotes suggests the existence of some protection against the AIDS progression (Dean et al., 1996; Huang et al., 1996; Michael et al., 1997). The CCR5∆32 allele is common in North America and Europe, with heterozygote frequencies varying from 10 to 20% in Caucasians (Dean et al., 1996; Huang et al., 1996; Liu et al., 1996; Samson et al., 1996b; Martinson et al., 1997). In Eurasia CCR5∆32 frequencies show a north-south gradient with the highest allele frequencies in Finnish and Mordvinian populations (16%) and the lowest in Sardinia (4%) (Libert et al., 1998). The CCR5∆32 allele is not found in aboriginal populations outside Eurasia (Martinson et al., 1997; Leboute et al., 1999; Lu et al., 1999). The presence of CCR5∆32 allele elsewhere throughout the world probably represents recent European gene flow into local populations (Martinson et al., 1997). The origin of the CCR5∆32 has been speculatively dated to approximately 700 years Frequency of the CCR5∆32 allele in Brazilians: a study in colorectal cancer and in HTLV-I infection