APOBEC3G genetic variants do not influence CD4 T cell counts, HIV viral load and are not associated with protection against HIV-1 infection
J.A. Vázquez Perez, G. Cerezo, C.E. Ormsby, R. Hernandez-Juan, K.J. Torres, G. Reyes-Teran
Instituto Nacional de Enfermedades Respiratorias, Centro de Investigación en Enfermedades Respiratorias, Mexico City, Mexico
Background: Human APOBEC3G (hA3G) is a potent inhibitor of HIV replication and has been considered as a cellular anti-HIV factor. Recently some reports demonstrated that genetic variation of hA3G may significantly affect HIV-1 pathogenesis or transmission. We analyzed the effects of 17 single nucleotide polymorphisms (SNPs) of both APOBEC3G regulatory and coding region that may modify the protein expression in a cohort of Mexican exposed seronegative cohort (ES) and their influence on progression in HIV infected patients.
Methods: Cohort study groups consisted of 54 ES, HIV infected patients at different stages of infection (n=48), HIV infected patients with persistent low viral load (n=12) and healthy control subjects (n=50). Nucleotide polymorphisms in regulatory region and H186R in the exon 4 were performed by sequencing. The genetic effects of SNPs on HIV-1 infection susceptibility or protection were assessed by comparing genotypic frequencies with hA3G mRNA expression, CD4 T cell count and viral load.
Results: We identified 16 SNPs within regulatory region of hA3G in our cohort. Nine of these SNPs were described previously and seven were novel. We found no significant difference in the distribution of SNPs between HIV-negative and HIV positive individuals or ES individuals. Also found no correlation between hA3G mRNA expression, CD4 T cells counts or HIV viral load and the presence or absence of SNPs in hA3G regulatory region. Moreover the variant, H186R that was previously shown to have AIDS-accelerating effects had a reduced allele frequency in our total cohort of 0.089 and had no significant association with HIV disease progression or protection.
Conclusions: In this cohort, we describe the frequencies of several SNPs and identify several novel SNPs, however our studies shows that genetic variants of hA3G do not affect HIV-1 pathogenesis and that others factors similar to epigenetic could be are implicated in the expression and function of hA3G.
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