Association between IRGM polymorphisms and tuberculosis risk: A meta-analysis

BACKGROUND: The human immunity-related GTPase M (IRGM) is involved in regulating autophagy against invading pathogens. Recently, inconsistent results have been reported about the association between IRGM polymorphisms and tuberculosis risk in several studies. METHODS: We searched the PubMed, Embase, and Web of Knowledge, and extracted data from eligible articles to estimate the associations between IRGM polymorphisms (rs10065172, rs4958842, rs4859843, rs4859846, and rs72553867) and tuberculosis risk. The pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated using Review manager 5.3. The studies heterogeneity was assessed by Cochran Q test. Funnel plot, Begg test, and Egger linear regression test were used to evaluate the publication bias. RESULTS: Nine case-control studies in 8 articles involving 3780 tuberculosis and 4835 control were analyzed. The analysis showed that IRGM rs10065172 and rs4859846 were significantly associated with tuberculosis risk in all genetic models whereas the latent tuberculosis infection group in 1 study was excluded. However, stratified analysis revealed significant associations for IRGM rs10065172 in all genetic models among Asians, but not for African/African-Americans. Significant associations were observed in recessive and dominant model for rs4958842, allele and recessive model for rs4859843, and all genetic models for rs4859846. No significant associations between rs72553867 polymorphism and tuberculosis risk was identified. Publication bias was detected in allele and additive model of rs4859843. CONCLUSIONS: IRGM rs10065172 was associated with decreased risk of tuberculosis in Asian populations, but not in African/Africa-Americans. rs4958842, rs4859843, and rs4859846, had a large protective effect in Asians, whereas rs72553867 was not associated with tuberculosis risk.