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IRGM genetic variants associate with tuberculosis disease in a European population
Tonino Alonzi1, Assunta Navarra2, Razaq Durodoye3
1Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, 00149 Rome, Italy.
Background:
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.
Objective:
To investigate whether two IRGM single-nucleotide polymorphisms (SNP), 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 TB patients, 194 TBI individuals, and 256 TB-free controls revealed no significant associations with TB status. However, diplotype analysis identified an association between the rs4958847-rs72553867 GG-AC vs GG-CC diplotype with TB diseases with respect to TB-free group (OR=2.56, 95% CI:1.18-5.56).
Conclusions:
Although the individual IRGM variants were not associated with TB, combined diplotype analysis indicated a potential role for IRGM-mediated autophagy in TB disease within European populations.
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