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Host genetic susceptibility to human tuberculosis

R J Bellamy1, A V Hill

  • 1Wellcome Trust Centre for Human Genetics, Oxford University, UK.

Novartis Foundation Symposium
|February 9, 1999
PubMed
Summary

Host genetics significantly impact tuberculosis outcomes. This study identified potential genetic links, including NR AMP1 and vitamin D receptor gene (VDR) polymorphisms, suggesting complex genetic control over tuberculosis susceptibility.

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Area of Science:

  • Genetics
  • Infectious Diseases
  • Immunology

Background:

  • Host genetic factors play a crucial role in determining susceptibility and resistance to infectious diseases like tuberculosis.
  • Understanding these genetic influences is vital for developing effective prevention and treatment strategies for tuberculosis.

Purpose of the Study:

  • To identify host genes that influence the outcome of human tuberculosis infection.
  • To investigate genetic associations with tuberculosis susceptibility using both genome-wide and candidate gene approaches.

Main Methods:

  • A linkage-based genome screen was conducted using 282 markers in 92 affected sib pairs.
  • An association-based candidate gene study examined polymorphisms in over 400 tuberculosis cases and 400 healthy controls.
  • Specific genes investigated included NR AMP1 and the vitamin D receptor gene (VDR).

Main Results:

  • The genome screen provided preliminary evidence for co-segregation of tuberculosis with five markers, though replication is needed.
  • No single major gene strongly linked to tuberculosis susceptibility was identified, indicating complex genetic control.
  • Polymorphisms in the NR AMP1 and vitamin D receptor gene (VDR) were found to be associated with tuberculosis.

Conclusions:

  • Tuberculosis susceptibility is polygenic, influenced by multiple host genes rather than a single major gene.
  • NR AMP1 and VDR gene polymorphisms represent potential genetic markers associated with tuberculosis.
  • Identifying these susceptibility genes may offer new avenues for therapeutic and preventative strategies against tuberculosis.

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