Association of TIRAP (rs8177374) and MyD88 (rs6853) genetic polymorphisms with susceptibility to pulmonary tuberculosis and treatment response

Abstract

Toll-like receptors (TLRs) identify some components of Mycobacterium TB, the main causative agent of tuberculosis. The signaling pathways causing activation of the immune response involve the MyD88 and TIRAP genes. We aimed to investigate the role of MyD88 (rs6853) and TIRAP (rs8177374) gene variants in pulmonary TB susceptibility and treatment response in a sample of Egyptian population. A case-control study followed by follow-up was conducted on 220 participants distributed as 110 newly diagnosed PTB patients, and 110 healthy controls. Patients and controls were subjected to genotyping of TIRAP (rs8177374) and MyD88 (rs6853) using real time PCR technique. Our results revealed that, Bacteriological tests Ziehl Neelsen smear microscopy was positive in 46.4% of patients, GeneXpert was positive in 70.9% of patients, bacterial culture of sputum was positive in 100.0% of patients. As regards rs6853, a significant increase of frequency of the mutant GG genotype and G allele observed among patients with pulmonary TB than controls (P = 0.001) with an increased risk of acquiring TB (OR = 4.88, CI95%: (2.31–10.28) and +3.21, CI95% 2.10–4.91 respectively). Additionally C/T polymorphism (rs8177374) at TIRAP gene showed a significant increase of frequency of the heterozygous mutant CT genotype and T allele in the patients than in the controls and showed higher association with TB (OR = 5.46, CI95%: (2.84–10.52) and 3.39, CI95% 2.22–5.19 respectively). MyD88 (rs6853) GG and TIRAP (rs8177374) CT genotypes showed the highest percentage of non-responders to treatment compared with other genetic variants. CT + GG and TT + GG reported high number of no response to treatment than other combinations. TIRAP rs8177374 CT and MyD88 rs6853 GG genotypes are associated with susceptibility to PTB in a sample of Egyptian population. Simultaneous genotyping of both genes could be considered as a genetic risk factor for PTB and predictor of the patient response to treatment.