ASSOCIATION OF MYCOBACTERIUM TUBERCULOSIS LINEAGES WITH IFN-Γ AND TNF-Α GENE POLYMORPHISMS AMONG PULMONARY TUBERCULOSIS PATIENT

Mohammad Varahram, Parissa Farnia, Mohammad Javad Nasiri, Mona Afraei Karahrudi, Mehdi Kazampour, Ali Akbar Velayati
  • Mohammad Varahram
    Mycobacteriology Research Centre, National Research Institute of Tuberculosis and Lung Disease [NRITLD], Masih Daneshvari Hospital , Shahid Beheshti University of Medical Sciences, Iran, Islamic Republic of
  • Parissa Farnia
    Mycobacteriology Research Centre, National Research Institute of Tuberculosis and Lung Disease [NRITLD], Masih Daneshvari Hospital , Shahid Beheshti University of Medical Sciences, | pfarnia@sbmu.ac.ir
  • Mohammad Javad Nasiri
    Mycobacteriology Research Centre, National Research Institute of Tuberculosis and Lung Disease [NRITLD], Masih Daneshvari Hospital , Shahid Beheshti University of Medical Sciences, Iran, Islamic Republic of
  • Mona Afraei Karahrudi
    Affiliation not present
  • Mehdi Kazampour
    Affiliation not present
  • Ali Akbar Velayati
    Affiliation not present

Abstract

The six major lineages of Mycobacterium tuberculosis [MTB] are found to be strongly associated with specific geographical outbreaks. But whether these bacterial lineages influence the host genetic polymorphism is uncertain. The present study was designed to evaluate the relevance of strain diversity and host genetic polymorphisms in susceptibility to pulmonary tuberculosis [PTB]. For this reason, single –nucleotide polymorphisms [SNPs] in interferon- γ [IFN-γ] receptor-1[G-611A], IFNG [G+ 2109A] and tumor necrosis factors [TNF-α] genes [at -238, 308,-857position] in patients [n=151] were analyzed and compared with controls [n=83]. The genetic diversity of M. tuberculosis isolates were performed using spacer oligonucleotide typing. Thereafter, the profile of IFN-γ and TNF-α allele frequency were investigated in each subtype of M .tuberculosis. The results showed C allele of TNF 857 and A allele of TNF 238 were more frequent in PTB cases [[TNF 857 C allele OR [CI95%] 0.6[0.4-0.9], p= 0.02] for TNF 238 A allele OR [CI95%] 5.5[3.4-9.0], p= 0.00]]. Similarly, G allele in IFNG+ 2109 A/G polymorphism were significantly more in patients than control subject[OR[CI95%] 0.3; p< 0.05]. The major identified clinical isolates of M. tuberculosis were EAI[42; 27.8% ], Haarlem[ 31; 20.5% ], CAS [ 23;15.2% ], Beijing[14; 9.2%], and T [11; 7.2%  ] lineages. No correction was observed between strains diversity and frequency of SNPs in studied PTB cases. In conclusions, we exclude the possibility of genetic mutation in IFN-γ and TNF-α gene by different subtypes of M .tuberculosis. Although, our results supports a positive correlation between host SNPs and susceptibility to PTB.

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Submitted: 2014-07-21 14:07:35
Published: 2014-02-16 00:00:00
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