Genetic polymorphism of toll-like receptors in HIV-I infected patients with and without tuberculosis co-infection.

Abstract

Toll-like receptors (TLRs) are identified as one of the key components of innate immune system due to their ability to sense conserved molecular motifs associated with several pathogens. It has been implicated from several evidence that mutations in genes encoding TLRs are associated with increased or decreased susceptibility to various infectious diseases. The study was prospective, cross-sectional, as well as longitudinal in nature, which includes 223 HIV-positive patients, 150 HIV-positive patients with latent tuberculosis (TB) infection, 150 HIV-positive patients with active TB, 200 HIV-negative newly diagnosed sputum smear positive pulmonary TB patients, and 205 healthy subjects. A statistically significant difference was observed in allelic frequencies of TLR4 between healthy subjects and HIV + TB patients (P < 0.001), healthy subjects, and pulmonary TB (PTB) Category-I patients (P < 0.01) and between healthy subjects and HIV + TB patients (P < 0.001). TLR4 genotype frequencies were also significantly different between healthy subjects and PTB Cat I patients (P < 0.001) and HIV + and HIV + TB patients (P < 0.01). A statistically significant difference was also observed between HIV + and PTB Cat I patients (P = 0.04), HIV + LTBI and HIV + TB patients (P = 0.01), and between HIV + TB and PTB Cat I patients (P < 0.01). This study implicates that Asp299Gly polymorphism in TLR4 gene is associated with increased susceptibility to active TB in HIV-seropositive patients. Increased frequency of 'A' allele in TLR9 gene was also discovered at the time of active TB development in ART naïve HIV + patients, who developed active TB on follow-up.