Association of Mycobacterium infections in patients with Mendelian susceptibility to mycobacterial disease with venous thromboembolism.
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.
Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases.
Maryam
M
Alinejad Dizaj
Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases.
Seyed Alireza
SA
Mahdaviani
Clinical Tuberculosis and Epidemiology Research Center, National Research Institute for Tuberculosis and Lung Diseases.
Payam
P
Tabarsi
Department of Food Science and Technology, Science and Research branch, Islamic Azad University, Tehran, Iran.
Hamed
H
Ahari
Department of Cellular and Molecular Biology, Endocrinology Research Center.
Ahmad
A
Ebrahimi
Virology Research Center, National Research Institute for Tuberculosis and Lung Diseases.
Seyed Alireza
SA
Nadji
Tobacco Prevention and Control Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Habib
H
Emami
Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases. Emortaz@gmail.com.|Clinical Tuberculosis and Epidemiology Research Center, National Research Institute for Tuberculosis and Lung Diseases. Emortaz@gmail.com.|Molecular Biology Group, Airways Disease Section, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London, UK. Emortaz@gmail.com.
Esmaeil
E
Mortaz
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D005165:Factor V / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009164:Mycobacterium Infections / Q000453:epidemiology / Q000209:etiology*; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012008:Recurrence; D054556:Venous Thromboembolism / Q000150:complications* / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
D016207:Cytokines; C095381:factor V Leiden; D005165:Factor V; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
MTHFR A1298C; MTHFR C677T; Mendelian susceptibility to mycobacterial disease; TNF-α