Cheng Li-Ping, Liu Zhi-Bin, Wang Lei, Cao Jie, Qu Qing-Rong, Lou Hai, Shen Xiao-Na, Yang Juan, Yu Yuanyuan, Zheng Rui Juan, Sha Wei, Sun Qin
Clinical and Research Center for Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
Inflamm Res. 2025 Jul 22;74(1):106. doi: 10.1007/s00011-025-02071-y.
To investigate the association of genetic polymorphisms in MB21D1 (Mab-21 domain-containing 1), TMEM173 (Transmembrane Protein 173), IFNB1 (Interferon beta 1), IFNGR1 (Interferon gamma receptor 1), IFNGR2 (Interferon gamma receptor 2), IRF3 (Interferon Regulatory Factor 3), and IRF8 (Interferon Regulatory Factor 8) with susceptibility to non-tuberculous mycobacteria pulmonary disease (NTM-PD) as well as their correlation with the treatment outcomes and immune status of patients.
Forty-four tagSNPs from the candidate genes were genotyped in a 2-phase cohort study including an initial discovery phase involving 707 NTM-PD patients and 726 healthy controls and a replication phase involving 357 NTM-PD patients and 400 controls. The frequencies and distributions of genotypes were compared between the case and control groups. Treatment success rates, sputum culture conversion rates, imaging characteristics, and peripheral blood immunological indices were compared among patients with different genotypes.
Individuals with the IFNGR1 rs2234711 A/A genotype were more susceptible to MAC-PD compared to those with the G/G genotype (discovery phase OR = 1.752, P.adj = 0.025; replication phase OR = 2.143, P.adj = 0.019). Patients with the rs2234711 A/A genotype exhibited significantly lower treatment success rates and sputum culture conversion rates, along with elevated levels of peripheral blood heparin-binding protein (HBP), erythrocyte sedimentation rate, and interleukin-10, but significantly decreased interleukin-1β levels (all P < 0.05). Individuals with the IRF8 rs2280378 A/A genotype were more susceptible to MAB-PD (discovery phase OR = 2.302, P.adj = 0.014; replication phase OR = 2.465, P.adj = 0.015). Compared to G/G genotype patients, those with the rs2280378 A/A genotype exhibited lower treatment success rates and sputum culture conversion rates, were more likely to develop pulmonary cavities and multiple lung field involvement, and showed elevated levels of peripheral blood HBP and C-reactive protein, along with significantly reduced levels of serum interleukin-12 P70, tumor necrosis factor-α, and CD8 + T lymphocytes (all P < 0.05).
In the Chinese Han population, IFNGR1 genetic polymorphisms are closely associated with MAC-PD susceptibility, while IRF8 genetic polymorphisms are associated with MAB-PD susceptibility. Variants in IFNGR1 and IRF8 significantly affect the immune status and treatment outcomes of MAC-PD and MAB-PD patients, respectively.
研究MB21D1（含Mab-21结构域蛋白1）、TMEM173（跨膜蛋白173）、IFNB1（干扰素β1）、IFNGR1（干扰素γ受体1）、IFNGR2（干扰素γ受体2）、IRF3（干扰素调节因子3）和IRF8（干扰素调节因子8）基因多态性与非结核分枝杆菌肺病（NTM-PD）易感性的关系，以及它们与患者治疗结局和免疫状态的相关性。
在一项两阶段队列研究中对候选基因的44个标签单核苷酸多态性（tagSNP）进行基因分型，第一阶段为发现阶段，纳入707例NTM-PD患者和726例健康对照；第二阶段为验证阶段，纳入357例NTM-PD患者和400例对照。比较病例组和对照组基因型的频率和分布。比较不同基因型患者的治疗成功率、痰培养转阴率、影像学特征和外周血免疫指标。
与携带G/G基因型的个体相比，携带IFNGR1 rs2234711 A/A基因型的个体更易患鸟分枝杆菌肺病（MAC-PD）（发现阶段：比值比[OR]=1.752，校正P值=0.025；验证阶段：OR=2.143，校正P值=0.019）。携带rs2234711 A/A基因型的患者治疗成功率和痰培养转阴率显著降低，外周血肝素结合蛋白（HBP）、红细胞沉降率和白细胞介素-10水平升高，但白细胞介素-1β水平显著降低（均P<0.05）。携带IRF8 rs2280378 A/A基因型的个体更易患脓肿分枝杆菌肺病（MAB-PD）（发现阶段：OR=2.302，校正P值=0.014；验证阶段：OR=2.465，校正P值=0.015）。与携带G/G基因型的患者相比，携带rs2280378 A/A基因型的患者治疗成功率和痰培养转阴率较低，更易出现肺空洞和多肺野受累，外周血HBP和C反应蛋白水平升高，血清白细胞介素-12 P70、肿瘤坏死因子-α和CD8+T淋巴细胞水平显著降低（均P<0.05）。
在中国汉族人群中，IFNGR1基因多态性与MAC-PD易感性密切相关，而IRF8基因多态性与MAB-PD易感性相关。IFNGR1和IRF8的变异分别显著影响MAC-PD和MAB-PD患者的免疫状态和治疗结局。
