Genetic Association and Expression Studies Indicate a Role of Toll-Like Receptor 8 in Pulmonary Tuberculosis
2008

Role of TLR8 in Pulmonary Tuberculosis

Sample size: 2211 publication 10 minutes Evidence: high

Author Information

Author(s): Sonia Davila, Martin L. Hibberd, Ranjeeta Hari Dass, Hazel E. E. Wong, Edhyana Sahiratmadja, Carine Bonnard, Bachti Alisjahbana, Jeffrey Szeszko, Yanina Balabanova, Francis Drobniewski, Reinout van Crevel, Esther van de Vosse, Sergey Nejentsev, Tom H. M. Ottenhoff, Mark Seielstad

Primary Institution: Genome Institute of Singapore

Hypothesis

Does genetic variation in the TLR8 gene influence susceptibility to pulmonary tuberculosis?

Conclusion

The study provides evidence that TLR8 gene polymorphisms are associated with increased susceptibility to pulmonary tuberculosis in males across different populations.

Supporting Evidence

  • Four TLR8 polymorphisms were associated with TB susceptibility in males.
  • The association was replicated in a Russian cohort.
  • TLR8 transcript levels were significantly up-regulated during active TB.
  • Increased TLR8 protein expression was observed in macrophages after infection.

Takeaway

Some people get sick from tuberculosis while others don't, and this study found that a specific gene, TLR8, might be a reason why.

Methodology

The study involved genotyping SNPs in TB patients and controls, followed by expression analysis of TLR8 in blood samples.

Potential Biases

Potential bias due to population stratification was addressed, but residual confounding cannot be completely ruled out.

Limitations

The study primarily focused on male subjects, which may limit the generalizability of the findings to females.

Participant Demographics

The study included 375 Indonesian TB patients and 1,837 Russian TB patients, with a majority being male.

Statistical Information

P-Value

0.007

Confidence Interval

1.2–2.7

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pgen.1000218

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