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CD209 genetic polymorphism and tuberculosis disease.

Fredrik O Vannberg1, Stephen J Chapman, Chiea C Khor

  • 1Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. fredrik.vannberg@well.ox.ac.uk

Plos One
|January 3, 2008
PubMed
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The CD209 -336G allele offers protection against tuberculosis in sub-Saharan Africa. Individuals with the -336GG genotype have a lower risk of severe cavitary tuberculosis, suggesting decreased DC-SIGN receptor levels are protective.

Area of Science:

  • Immunogenetics
  • Infectious Diseases
  • Genomics

Background:

  • Tuberculosis (TB) remains a major global health challenge, particularly in sub-Saharan Africa.
  • DC-SIGN (CD209) is a receptor involved in Mycobacterium tuberculosis interaction.
  • The CD209 promoter -336A/G single nucleotide polymorphism (SNP) has been linked to susceptibility to various infections.

Purpose of the Study:

  • To investigate the association of the CD209 -336A/G variant with tuberculosis susceptibility in a large sub-Saharan African population.
  • To determine if this genetic variant influences the risk of developing severe forms of tuberculosis, such as cavitary disease.

Main Methods:

  • Genotyping of the CD209 -336A/G SNP (rs4804803) in 2,176 individuals from case-control studies in four sub-Saharan African countries.

Related Experiment Videos

  • Statistical analysis, including Mantel-Haenszel and Pearson's chi-squared tests, to assess the association between the SNP and tuberculosis risk.

    • Main Results:

    • The -336G allele was associated with significant overall protection against pulmonary tuberculosis (OR=0.86, P=0.006).
    • Individuals with the -336GG genotype showed a significantly decreased risk of cavitary tuberculosis (OR=0.42, P=0.00003).
    • These findings align with previous observations of the protective effect of the -336G allele.

    Conclusions:

    • The CD209 -336G variant allele confers significant protection against tuberculosis in sub-Saharan African populations.
    • The -336GG genotype is linked to a reduced likelihood of developing lung cavitation in tuberculosis patients.
    • Down-regulation of CD209 mRNA expression by the -336G allele suggests decreased DC-SIGN receptor levels may protect against tuberculosis, potentially by limiting pathogen-induced immune suppression.