Association of APOBEC3G polymorphisms and hypermutation levels with AIDS progression among Brazilian individuals
M.C. Bizinoto1, E. Leal2, M. Leão1, E. Morais1, L.M. Janini1
1Federal University of Sao Paulo, Infectology, Sao Paulo, Brazil, 2Federal University of Para, Institute of Biotechnology, Belém, Brazil
Background: APOBEC3G (A3G) has been described as a host factor that inhibits HIV-1 replication. During reverse transcription, A3G promotes the deamination of cytidines to uridines in the nascent minus-strand viral DNA, inducing G-to-A hypermutation in the plus-strand. Although a few single nucleotide polymorphisms (SNPs) have been described occurring along A3G gene their effects on HIV-1 disease progression is not clear. This study attempted to establish, in the Brazilian population, the frequencies of 7 previously described A3G SNPs and its impact on viral loads and TCD4 cells counts, in association with the presence of hypermutation in the integrase gene.
Methods: 400 seropositive drug naïve patient were analyzed. A3G SNPs were detected by resequencing. Hypermutation was investigated using the bisbenzimide-PEG dye during electrophoresis runs on agarose gels. Gels were analyzed using the Image J software and according to the position of bands when compared to controls, samples were categorized.
Results: SNPs frequencies showed to be under the Hardy-Weinberg equilibrium. The relative linkage disequilibrium was statistically significant in all pair of locus. SNP frequencies in the Brazilian population was closer to Europeans than Africans. We found a low frequency (2%) of the H186R SNP, previously associated with accelerated disease progression, when compared to its frequency in a African cohort (22%). This find is in agreement with historical records, which show the importance of the European contribution to Brazilian population. We were able to detect hypermutation in 36% of samples, but we not observed correlation between A3G SNP composition and hypermutation, viral loads or TCD4 cells counts.
Conclusions: The genotypic frequencies of A3G in Brazilians is similar to Europeans. Genetic variation of A3G may affect HIV-1 pathogenesis, but we not found association with hypermutation levels,and the association analysis revealed lack of influence of A3G polymorphisms to the viral load and CD4+ T lymphocytes cells count.
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