Study of HLA and microsatellite markers polymorphisms in the HIV-1 disease.
[INTRODUCTION] Host genetic factors can play an important role in mediating resistance to HIV-1 infection and delayed of the course of infection. HLA polymorphism is an importantdeterminant in the HIV-1 infection and AIDS. HLA class I genes are prominents in AIDS association studies. The information about the HLA profiles in different populationscontribute to better knowledge of the outcome of HIV-1 infection and for therapeutic strategies and prophylactic AIDS vaccine guiding. [OBJEVTIVE] To identify genetic polymorphisms in the MHC locus and to investigate associations with AIDS pathogenesis in HIV-1 infected individuals in the Salvador-BA population.[MATERIAL AND METHODS] MHC markers (microsatellite markers D6S105 (class I), DRACA (class II) and TNF-d, (class III) and HLA-A, B and C genes) genotyping was performed by using two different methods, both previously by PCR. After PCR, amplification products were separeted by capillary electrophoresis. Alleles were designed according to the amplified fragment´s size. HLA class I was performed by hibridization with sequence-specific oligonucleotide probes following amplification of the corresponding HLA-A, -B and ?C genes. The results were interpreted using a software that established the HLA genotyping. Statistical analysis was performed using Fisher´s exact test and Mann-Whitney test for categorical and continuous variables, respectively.[RESULTS] We found no association of MHC markers with disease progression of HIV-1 infection. Our results suggest association of TNF-d microsatellite with resistance to HIV-1 infection and modulation of the plasm viral load and TCD4+ cell count. We alsoobserved HLA class I alleles (HLA-A*26, -A*31, -A*66, -A*69, -A*74 and -A*80; HLAB* 27, -B*40, -B*51, -B*57 and -B*81; and HLA-Cw*01, -Cw*15 and -Cw*18) and Bw4 sorological epitope associated with clinical predictors modulation of the course of HIV-1 infection. [CONCLUSION] We conclude that MHC polymorphism (TNF-d microsatellite, HLA-A, HLA-B and HLA-C) provide a important protective role in AIDS pathogenesis by modulating the plasm viral load and TCD4+ cell count.
Advisor:Angelina Xavier Acosta; Bernardo Gavão Castro
School:Faculdades Oswaldo Cruz
Source Type:Master's Thesis
Keywords:Acquired Immunodeficiency Syndrome Polymorphism Genetic Genes MHC Class I II HLA Antigens Microsatellite Repeats
Date of Publication:02/11/2008