The impact of common Smurf1 gene variants on the risk, clinical characteristics and short-term prognosis of tuberculous meningitis.

• Smurf1 represents a key component in anti-tuberculous host defense. • We hypothesized genetic variants in the Smurf1 gene impact susceptibility to TBM. • The variants of Smurf1 were associated with the incidence of TBM. • The Smurf1 variants were not correlated to the severity or prognosis of TBM. • This indicated an important role for Smurf1 in the immunopathogenesis of TBM. Tuberculous meningitis (TBM) is the most severe form of infection caused by Mycobacterium tuberculosis (Mtb). Smurf1 represents a key component in anti- Mtb autophagic targeting in macrophages and in anti-TB host defense in vivo. We hypothesized that genetic variants in the Smurf1 gene region influence susceptibility to TBM. Using a case-control study design (235 TBM cases, 239 pulmonary TB cases and 478 healthy controls), we evaluated whether 8 haplotype-tagging single nucleotide polymorphisms (SNPs) in the Smurf1 gene are associated with the development of TBM. Even with the most conservative correction, the polymorphism rs6956450 was associated with TBM under a dominant model (odds ratio [OR], 1.653; 95% confidence interval [CI], 1.192–2.294; P = 0.021), the CG haplotype consisting of rs3294 and rs6956450 was positively associated with TBM (P = 0.013) and another haplotype GC remained negatively associated with TBM in Tibetan subgroup (P < 0.001). No correlation was found between rs6956450 and TBM clinical characteristics or prognosis. These results firstly link the variants in the Smurf1 gene region with TBM risk, indicating an important role for Smurf1 in the immunopathogenesis of TBM. Future studies will dissect the mechanism, which may help identify targets or genetic markers to guide diagnosis or host-directed therapy in patients with TBM. [ABSTRACT FROM AUTHOR]