Association of IRGM Polymorphisms and Susceptibility to Pulmonary Tuberculosis in Zahedan, Southeast Iran

Abstract

Tuberculosis (TB) is a major cause of morbidity and mortality worldwide. IRGM1 is an important protein in the innate immune response against intracellular pathogens by regulating autophagy. Polymorphisms in the IRGM genes are known to influence expression levels and may be associated with outcome of infections. This case-control study was done on 150 patients with PTB and 150 healthy subjects to determine whether the IRGM polymorphisms at positions −1208 A/G (rs4958842), −1161 C/T (rs4958843), and −947 C/T (rs4958846) were associated with PTB. The polymorphisms were determined using tetra-amplification refractory mutation system-PCR (T-ARMS-PCR). The results showed that the IRGM −1161 C/T and −947 C/T polymorphisms were associated with decreased susceptibility to PTB (OR = 0.06, 95% CI = 0.03–0.13, P < 0.001 and OR = 0.27; 95% CI = 0.013–0.55, P < 0.001, resp.). No significant difference was found among the groups regarding −1208 A/G polymorphism. In conclusion we found that the IRGM −1161 C/T and −947 C/T polymorphisms but not −1208 A/G polymorphism provide relative protection against PTB in a sample of Iranian population.

Resistance to cellular autophagy by Mycobacterium tuberculosis Beijing strains

“…23 Moreover, polymorphisms in the human autophagy and autophagy-related genes IRGM and P2X7 are found to be associated with susceptibility to tuberculosis. [24][25][26][27][28] All of these data underscore the importance of autophagic process in mycobacterial control and indicate that the magnitude of autophagic elimination of mycobacteria may be the key determinant of their virulence and pathogenesis.…”

Autophagy in the Fight Against Tuberculosis

“…Although the detailed mechanism by which this gene regulates autophagy is not clear, IRGM was shown to induce clearance of mycobacteria in infected macrophages by inducing phagosomal maturation and autophagy. Most of the variants are associated with increased protection against TB (Intemann et al, 2009;Che et al, 2010;Bahari et al, 2012). However, carriers of the Chron's disease-related T allele of rs10065172 reveal increased susceptibility to TB (King et al, 2011), while the -1208G/ -1161T/ -947T haplotype is also positively associated with the disease (Che et al, 2010).…”

Autophagy in Tuberculosis

“…For example, polymorphisms in ATG16L1 and IRGM, have been initially identified through GWASs as autophagy risk loci for Crohn's disease (Wellcome Trust Case Control Consortium 2007), a common form of IBD. Subsequent human population studies have shown that IRGM, encoding an autophagy-modulating factor (Singh et al 2006, is also a risk factor for tuberculosis (Intemann et al 2009;Che et al 2010;King et al 2011;Bahari et al 2012). …”