Partial protective effect of CCR5-Delta 32 heterozygosity in a cohort of heterosexual Italian HIV-1 exposed uninfected individuals |
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Authors: | Enrico M Trecarichi Mario Tumbarello de Gaetano Katleen Donati Enrica Tamburrini Roberto Cauda Christina Brahe Francesco D Tiziano |
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Institution: | (1) Department of Infectious Diseases, Catholic University, Rome, Italy;(2) Department of Medical Genetics, Catholic University, Rome, Italy |
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Abstract: | Despite multiple sexual exposure to HIV-1 virus, some individuals remain HIV-1 seronegative (exposed seronegative, ESN). The
mechanisms underlying this resistance remain still unclear, although a multifactorial pathogenesis can be hypothesised. Although
several genetic factors have been related to HIV-1 resistance, the homozigosity for a mutation in CCR5 gene (the 32 bp deletion, i.e. CCR5-Delta32 allele) is presently considered the most relevant one. In the present study we
analysed the genotype at CCR5 locus of 30 Italian ESN individuals (case group) who referred multiple unprotected heterosexual intercourse with HIV-1 seropositive
partner(s), for at least two years. One hundred and twenty HIV-1 infected patients and 120 individuals representative of the
general population were included as control groups. Twenty percent of ESN individuals had heterozygous CCR5-Delta 32 genotype,
compared to 7.5% of HIV-1 seropositive and 10% of individuals from the general population, respectively. None of the analysed
individuals had CCR5-Delta 32 homozygous genotype. Sequence analysis of the entire open reading frame of CCR5 was performed in all ESN subjects and no polymorphisms or mutations were identified. Moreover, we determined the distribution
of C77G variant in CD45 gene, which has been previously related to HIV-1 infection susceptibility. The frequency of the C77G
variant showed no significant difference between ESN subjects and the two control groups. |
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