Association between SNPs in microRNA-machinery genes and tuberculosis susceptibility in Chinese Tibetan population

Tuberculosis (TB) is caused by infection with Mycobacterium tuberculosis and remains a leading cause of morbidity and mortality caused by infectious agents worldwide. Although our current understanding of the pathogenesis of TB is far from clear, there is a growing body of evidence suggesting a genetic contribution to the etiology of TB. By analyzing 294 TB cases and 287 healthy controls in a Chinese Tibetan population, we used a candidate gene approach to evaluate the association between six single nucleotide polymorphisms (rs10719, rs3757, rs3742330, rs636832, rs7813, and rs3744741) in microRNA machinery genes and TB susceptibility. The genotypic distributions of rs3757 and rs3744741 in controls were not in accordance with the Hardy-Weinberg Equilibrium (P < 0.05). Logistic regression analysis demonstrated that subjects carrying rs3742330 GG genotype had significantly decreased risk for TB than individuals carrying AA genotype [odds ratio (OR) = 0.31, 95 % confidence interval (CI) 0.12-0.75, P = 0.004. Carrying the G allele of rs3742330 was associated with a 27 % decreased risk for TB (95 % CI 0.55-0.97, P = 0.03). However, no significant associations were found for rs10719, rs636832 and rs7813. Computational modeling suggests that the rs3742330 lies within a predicted binding site (seed region) for microRNA-632 (miR-632) and that the G allele alters the affinity of microRNA-mRNA binding by disrupting the local structure of dicer 1, ribonuclease type III (DICER) mRNA, presumably allowing for upregulated DICER expression. Taken together, our data suggest that common genetic variations DICER may influence TB risk, possibly through miR-632-mediated regulation. Replication of our studies in other populations will strengthen our understanding of this association.