Association of Interferon- γ Receptor-1 Gene Polymorphism with Nontuberculous Mycobacterial Lung Infection among Iranian Patients with Pulmonary Disease

Abstract

Nontuberculous mycobacteria (NTM) cause significant pulmonary infections in humans. Researchers have reported an association between interferon-gamma receptor-1 (IFN-γR1 or IFNGR1) deficiency and susceptibility to NTM, but the relevance of polymorphism within these genes is not yet clear. In this study, a single nucleotide polymorphism (SNP), T to C, at position-56 in NTM patients with pulmonary disease was investigated. Molecular identification of Mycobacterium isolates was performed with hsp65 genes using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Then, the host genomic DNA from confirmed NTM patients (N = 80) and control subjects (N = 80) were screened for SNPs of IFNGR1 (T-56C) by PCR-RFLP. The results indicated that NTM patients had higher TC (26/80; 32.5%) or CC (46/80; 57.5%) genotypes in comparison with control groups (TC genotypes [22/80, 27.5%]; CC genotypes [6/80, 7.5%]) (P < 0.05). In this regard, all the patients infected with rapid-growing Mycobacterium (RGM, i.e., Mycobacterium chelonae and Mycobacterium fortuitum) had CC genotypes (100%). In contrary, only 50.7% (35/69) of infected patients with slow-growing Mycobacterium (i.e., Mycobacterium simiae, Mycobacterium kansasii, and Mycobacterium avium-intracellulare) had CC genotypes. Thus, patients with CC mutation in IFNGR1 at position-56 are more likely to develop RGM infection. In overall, there is a significant association between SNP of IFNGR1 at position-56 and susceptibility to NTM infection. Based on these data, we propose SNP of IFNGR1 at position-56 as a suitable "biomarker" for identifying populations at higher risk of infection.

Figure 1.

The pattern of Mycobacterium isolates that were characterized using hsp65 genes spacer polymerase chain reaction restriction fragment length polymorphism.

Figure 2.

The electrophoresis pattern of polymerase chain reaction (PCR) restriction fragment length polymorphism of single nucleotide polymorphisms of interferon-gamma receptor-1 (IFNGR1) at position-56. The PCR product is 455 base pairs (bp) (line 1). After digestion with Bst1, three genotypes were obtained: TT (line 3 = 313 + 215 + 142 bp), TC (lines 2 and 5 = 455 + 313 + 216 + 142 bp), and CC (lines 4 and 6 = 455 + 215 bp).