The association of CD209 promoter variants with tuberculosis infection susceptibility, AIDS development, and treatment response outcomes among an HIV-1 Moroccan population

Abstract

Transmission of Human immunodeficiency virus type 1 (HIV-1) to permissive CD4+T cells requires the dissemination of virus from sites of infection to secondary lymphoid organs, where extensive viral replication occurs in CD4+T cells. Several studies demonstrated that DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) molecules located on the surface of Dendritic Cell subsets showed high-affinity binding to HIV-1 and Mycobacterium tuberculosis (Mtb). It is exploited by HIV-1 and Mtb as a part of their immune evasion strategy. In this study, we investigated the possible involvement of DC-SIGN encoding gene CD209 variants in the development of tuberculosis (TB) among HIV-1 infected patients as well as AIDS development and treatment response outcomes in a Moroccan population. Two single nucleotide polymorphisms in the CD209 promoter − 336A > G (rs4804803) and − 139G > A (rs2287886) were investigated. Two hundred eighteen Moroccan subjects living with HIV-1 were genotyped using direct DNA sequencing. Out of 218 patients, 90 were co-infected with Mtb. Stratification of patient was performed according to TB status: as HIV-1+/TB- and HIV-1+/TB+ patients and their AIDS status as: AIDS and Non-AIDS patients. Our results revealed that genotype and allele frequencies of the − 336A > G and − 139G > A polymorphisms were not significantly different between HIV-1+/TB- and HIV-1+/TB+ patients (p > 0.05). Likewise, the development of AIDS doesn’t appear to be affected by these two SNPs either (p > 0.05). Haplotype analysis showed that none of the 4 possible haplotypes is associated with HIV-1 and TB co-infection (p > 0.05). Interestingly, the analysis of the − 139 G > A genotype distribution according to the HIV-1 viral load showed an improvement in AG and GG patients, after ART, compared to AA patients (p = 0.0069 and p = 0.0476; respectively). Overall, -336A > G and − 139G > A polymorphisms don’t influence the susceptibility of HIV-1 infected individuals to develop TB and AIDS. However, -139G > A polymorphism may affect the response to treatment as measured by RNA viral load levels. Further investigations are needed for a better understanding of the role of DC-SIGN in HIV-1 infection to provide new therapeutic pathways.