常见 Smurf1 基因变异对结核性脑膜炎发病风险、临床特征及短期预后的影响。

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

机构信息

Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, No. 37, Guo Xue Alley, Chengdu 610041, China.

出版信息

Int J Infect Dis. 2021 May;106:115-122. doi: 10.1016/j.ijid.2021.03.007. Epub 2021 Mar 9.

DOI:10.1016/j.ijid.2021.03.007

PMID:33711518

Abstract

OBJECTIVES

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

目的

结核性脑膜炎（TBM）是由结核分枝杆菌（Mtb）引起的最严重的感染形式。Smurf1 是巨噬细胞中抗 Mtb 自噬靶向和体内抗结核宿主防御的关键组成部分。我们假设 Smurf1 基因区域的遗传变异影响 TBM 的易感性。

方法

采用病例对照研究设计（235 例 TBM 病例、239 例肺结核病例和 478 例健康对照），评估 Smurf1 基因中 8 个单核苷酸多态性（SNP）的单倍型标签是否与 TBM 的发生有关。

结果

即使经过最保守的校正，多态性 rs6956450 在显性模型下与 TBM 相关（比值比 [OR]，1.653；95%置信区间 [CI]，1.192-2.294；P=0.021），由 rs3294 和 rs6956450 组成的 CG 单倍型与 TBM 呈正相关（P=0.013），另一种单倍型 GC 在藏族亚组中仍与 TBM 呈负相关（P<0.001）。rs6956450 与 TBM 临床特征或预后之间无相关性。