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

Microbiol Immunol. 2016 Oct;60(10):678-686. doi: 10.1111/1348-0421.12442.

Abstract

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.

Keywords: MTHFR A1298C; MTHFR C677T; Mendelian susceptibility to mycobacterial disease; TNF-α.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cytokines / blood
  • Cytokines / metabolism
  • Factor V / genetics
  • Female
  • Gene Frequency
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Middle Aged
  • Mutation
  • Mycobacterium Infections / epidemiology
  • Mycobacterium Infections / etiology*
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Prevalence
  • Recurrence
  • Venous Thromboembolism / complications*
  • Venous Thromboembolism / genetics*
  • Venous Thromboembolism / immunology
  • Young Adult

Substances

  • Cytokines
  • factor V Leiden
  • Factor V
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)