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No associations of human pulmonary tuberculosis with Sp110 variants
  1. T Thye1,
  2. E N Browne2,
  3. M A Chinbuah3,
  4. J Gyapong3,
  5. I Osei3,
  6. E Owusu-Dabo4,
  7. S Niemann5,
  8. S Rüsch-Gerdes5,
  9. R D Horstmann1,
  10. C G Meyer1
  1. 1Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
  2. 2Department of Community Health, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
  3. 3Health Research Unit, Ministry of Health, Accra, Ghana
  4. 4Kumasi Centre for Collaborative Research in Tropical Medicine, Kumasi, Ghana
  5. 5National Reference Center for Mycobacteria, Research Center Borstel, Borstel, Germany
  1. Correspondence to:
 Dr Christian G Meyer
 Bernhard Nocht Institute for Tropical Medicine, Department of Molecular Medicine, Bernhard Nocht Str. 74, 20359 Hamburg, Germany; c.g.meyer{at}bni.uni-hamburg.de

Abstract

Background: After a recent report on the role of the Ipr1 gene in mediating innate immunity in a mouse model of Mycobacterium tuberculosis infection, the human Ipr1 homologue, Sp110, was considered a promising candidate for an association study in human tuberculosis.

Methods: In a sample of >1000 sputum positive, HIV negative West African patients with pulmonary tuberculosis and >1000 exposed, apparently healthy controls, we have genotyped 21 Sp110 gene variants that were either available from public databases, including HapMap data, or identified by DNA re-sequencing.

Results: No significant differences in the frequencies of any of the 21 variants were observed between patients and controls. This applied also for HapMap tagging variants and the corresponding haplotypes, when including sliding window analyses with three adjacent variants, and when stratifying controls for positivity and negativity according to the results of intradermal tuberculin (purified protein derivative, PPD) skin tests. DNA re-sequencing revealed 13 novel Sp110 variants in the 5′-UTR, exons, and adjacent intronic regions.

Conclusions: Based on the results obtained in this case-control study, the hypothesis that Sp110 variants and haplotypes might be associated with distinct phenotypes of human M tuberculosis infection is doubtful.

  • DOTS, Directly Observed Treatment Short-course strategy
  • FRET, fluorescence resonance energy transfer
  • GRR, genotype relative risk
  • Ipr1, intracellular pathogen resistance-1 gene
  • PPD, purified protein derivative
  • SAND, Sp100, AIRE-1, NucP41/75, and DEAF-1/suppressin
  • sst, super-susceptibility to tuberculosis
  • innate resistance
  • interferon-inducible gene
  • PPD
  • purified protein derivative

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Footnotes

  • The study has been supported by the German National Genome Research Network (project NIE-S17T20)

  • Competing interests: none declared

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