IRGM genetic variants associate with tuberculosis disease in a European population.

OBJECTIVES

Autophagy is a key host defense mechanism against Mycobacterium tuberculosis (Mtb). The autophagy-regulating gene, immunity-related GTPase M (IRGM), may influence tuberculosis (TB) susceptibility. To investigate whether two IRGM single-nucleotide polymorphisms (SNPs), rs4958847 and rs72553867, are associated with TB disease and/or TB infection (TBI).

METHODS

An unmatched case-control study was conducted at the National Institute of Infectious Diseases L. Spallanzani-IRCCS, Italy. Logistic regression analyses evaluated the effects of individual SNPs and their diplotypes on TB status.

RESULTS

Among 709 participants enrolled in Italy with diverse European ancestries, 644 individuals with complete data were included. Individual SNP analysis of 194 patients with TB disease, 194 individuals with TBI, and 256 TB-free controls revealed no significant associations with TB status. However, diplotype analysis identified an association between the rs4958847-rs72553867 GG-AC diplotype (reference category: GG-CC) and TB disease with respect to the TB-free group (odds ratio 2.56, 95% confidence interval 1.18-5.56).

CONCLUSIONS

Although the individual IRGM variants were not associated with TB, a combined diplotype analysis indicated a potential role for IRGM-mediated autophagy in TB disease in European populations.