Association of Mycobacterium infections in patients with Mendelian susceptibility to mycobacterial disease with venous thromboembolism

Maryam Alinejad Dizaj, Seyed Alireza Mahdaviani, Payam Tabarsi, Hamed Ahari, Ahmad Ebrahimi, Seyed Alireza Nadji, Habib Emami and Esmaeil Mortaz

Pediatric Respiratory Diseases Research Centre, NRITLD, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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 mycobacteriuminfected 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-a concentrations were quantified using a commercially available ELISA kit. Significant associations between mycobacterial infection and TNF-a production after stimulating peripheral blood mononuclear cells with LPS alone and with IFN-g 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.
Keywords: Mendelian susceptibility to mycobacterial disease, MTHFR A1298C, MTHFR C677T, TNF-a

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Microbiol Immunol 2016; 60: 678–686