XVIII International AIDS Conference

Abstract

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Single nucleotide polymorphisms (SNPs) in cytokine-coding genes in HIV-infected patients from Brazil

A.R.O. Léda1, A.N. Barbosa2, R.A.M.B. Almeida2, L.R. Souza2, D.A. Meira2, D. Elgui de Oliveira1

1Sao Paulo State University, Department of Pathology, Botucatu, Brazil, 2Sao Paulo State University, Department of Tropical Diseases and Image Diagnosis, Botucatu, Brazil

Background: The natural history of HIV infection and its progression towards aids may vary considerably among individuals. One of the possible reasons for this are genetic factors, including single nucleotide polymorphisms (SNPs). SNPs in promoters of cytokines genes may affect the immune system, but their impact on the course of HIV infection is currently under investigation. The present study aimed to evaluate the frequencies and possible effects of SNPs at positions -589 and -1098 in the IL-4 gene (SNP/pIL-4 -589 and SNP/pIL-4 -1098, respectively) and -238 and -862 in the TNF-α gene (SNP/pTNF-α -238 and SNP/pTNF-α -862, respectively) in HIV-infected patients from Brazil.
Methods: DNA samples from 157 patients were extracted from peripheral blood mononuclear cells. SNPs genotyping was performed by Real-time PCR-coupled High Resolution Melting analysis (HRM), along with controls validated by automated DNA sequencing.
Results: Patients carrying TT at SNP/pIL-4 -589 had lower circulating T CD8+ lymphocytes (mean= 841.6 cells/mm3, SD= 393.7 cells/mm3) compared to CC carriers (mean= 1,224.0 cells/mm3, SD= 1,125.0 cells/mm3) (p= 0.0104). On the other hand, carriers of TT at SNP/pIL-4 -1098 had higher circulating T CD8+ lymphocytes (mean= 1,146.7 cells/mm3, SD= 852.6 cells/mm3) compared to GT carriers (mean= 752.5 cells/mm3, SD= 299.6 cells/mm3) (p= 0.0053). Regarding the SNP/pTNF-α -238, GG and GA proportions were significantly different between patients without antiretroviral treatment (65% and 35%, respectively) and under treatment and without therapeutic failure (87.5% and 12.5%, respectively) (p= 0.0205). None of the other associations evaluated (between the SNPs and age, sex, route for HIV infection, sexual orientation, estimated time of HIV infection, CDC stage, T CD4+ cells counts, or HIV viremia) was significant.
Conclusions: The results provide compelling evidence that the presence of SNPs in cytokine-coding genes have an impact on the natural history of HIV infection, possibly due to changes in the balance between pro- and anti-inflammatory cytokines.


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