Alinejad Dizaj Maryam, Mahdaviani Seyed Alireza, Tabarsi Payam, Ahari Hamed, Ebrahimi Ahmad, Nadji Seyed Alireza, Emami Habib, Mortaz Esmaeil
Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases.
Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases.
Microbiol Immunol. 2016 Oct;60(10):678-686. doi: 10.1111/1348-0421.12442.
An association between a hypercoagulable state and Mendelian susceptibility to mycobacterial disease (MSMD) has been established in a few studies; resultant thrombosis is considered rare. In a case-control study, the prevalence of factor V Leiden, prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C mutations were investigated in mycobacterium-infected patients. The study comprised 30 patients with mycobacterial infections (invasive, disseminated and/or recurrent infections with Bacille Calmette-Guerin or non-tuberculosis mycobacteria and Mycobacterium Tuberculosis with positive results for acid-fast bacilli and tuberculin skin tests) and 30 normal healthy controls. Forty female (66.7%) and 20 male subjects (33.3%) aged from 3 to 70 years were recruited into this study. Genotyping of targeted genes was performed by RT-PCR and cytokine TNF-α concentrations were quantified using a commercially available ELISA kit. Significant associations between mycobacterial infection and TNF-α production after stimulating peripheral blood mononuclear cells with LPS alone and with IFN-γ plus LPS were identified. Moreover, genotyping analysis in the studied population revealed a significant association between MTHFR c.677C>T (OR, 3.28; 95% CI, 1.35-7.92; P < 0.05), MTHFR c.1298A>C (OR, 2.33; 95% CI, 1.10-4.93; P < 0.05) and mycobacterial infection in affected patients, indicating susceptibility to venous thromboembolism according to previous studies. Additionally, mycobacterium-infected patients had a significantly greater prevalence of MTHFR C677T and A1298C mutations than controls.
一些研究已证实高凝状态与孟德尔遗传性分枝杆菌病易感性（MSMD）之间存在关联；由此导致的血栓形成被认为较为罕见。在一项病例对照研究中，对分枝杆菌感染患者进行了因子V莱顿突变、凝血酶原G20210A突变以及亚甲基四氢叶酸还原酶（MTHFR）C677T、A1298C突变的患病率调查。该研究纳入了30例分枝杆菌感染患者（卡介苗或非结核分枝杆菌以及结核分枝杆菌引起的侵袭性、播散性和/或复发性感染，抗酸杆菌和结核菌素皮肤试验结果呈阳性）以及30名正常健康对照者。本研究招募了年龄在3至70岁之间的40名女性（66.7%）和20名男性受试者（33.3%）。通过逆转录聚合酶链反应（RT-PCR）对靶向基因进行基因分型，并使用市售酶联免疫吸附测定（ELISA）试剂盒对细胞因子肿瘤坏死因子-α（TNF-α）浓度进行定量。研究发现，仅用脂多糖（LPS）刺激外周血单个核细胞以及用γ干扰素（IFN-γ）加LPS刺激后，分枝杆菌感染与TNF-α产生之间存在显著关联。此外，对研究人群的基因分型分析显示，MTHFR c.677C>T（比值比[OR]，3.28；95%置信区间[CI]，1.35 - 7.92；P < 0.05）、MTHFR c.1298A>C（OR，2.33；95% CI，1.10 - 4.93；P < 0.05）与受影响患者的分枝杆菌感染之间存在显著关联，根据以往研究表明其对静脉血栓栓塞具有易感性。此外，分枝杆菌感染患者中MTHFR C677T和A1298C突变的患病率显著高于对照组。
