Association of Tumor Necrosis Factor-α (TNFα) Gene Polymorphisms with HLA Class II Alleles in HIV/AIDS Patients

Abstract

Aim of Study: To identify the factors of molecular genetic risks during the development of infection in HIV, based on the TNFα cytokine gene polymorphism in combination with HLA DRB1/DQA1/DQB1 genes, as well as to analyse their possible association with the progress of the disease. 185 HIV infected patients and 173 individuals control group have been analysed. The DNA was extracted from peripheral blood, by using QiagenQIAamp DNA kit reagents. The quality and quantity of DNA was checked by using Qubit ® fluorometer HLA typing for HLA DRB1/DQB1/DQA1* was performed by RT-PCR with sequence-specific primers (SSO). TNFα gene G–238A and G–308A polymorphic variant incidence was determined by RT-PCR analysis. Results: We have detected TNFα gene allele 308A in 11% HIV infected patients, whereas in control group this allele have been detected only in 4% patients. Although the incidence of the TNFα gene –238A allele was twice as high in the control group (6%) as in the HIV infected patients (3%), it did not prove to be statistically valid (p = 0.253). The incidence analysis of three-locus haplotypes DRB1-DQB1-DQA1 – in TNFα position-238A/G -308A/G showed that haplotypes 01:01/05:01/01:01-TNFα-238(GA)/308(GG) and 01:01/03:02/03:01 - TNFα-238(AA)/308(GG) are more frequent in the control group in comparison to the groups of infected patients. This means that these haplotypes have a protective function, which significantly affects the progress of infection. The association of 15:01/05:01/01:01 -TNFα-238(GG)/308(GG) and 03:01/05:01/01:01- TNFα-238(GG)/308(GА) genotypes indicates a high risk of developing a fulminant infection. The genetic factors of AIDS-related complex of syndromes development are associated not only with the HLA complex class II alleles, but also with the SNP polymorphism in the promoter region of cytokine genes.