Identification of Tuberculosis Susceptibility Genes with Human Macrophage Gene Expression Profiles
2008

Identifying Genes Linked to Tuberculosis Susceptibility

Sample size: 46 publication 10 minutes Evidence: moderate

Author Information

Author(s): Thuong Nguyen Thuy, Sarah J. Dunstan, Tran Thi Hong Chau, Vesteinn Thorsson, Cameron P. Simmons, Quyen Nguyen Than Ha, Guy E. Thwaites, Thi Ngoc Lan Nguyen, Martin Hibberd, Yik Y. Teo, Mark Seielstad, Alan Aderem, Jeremy J. Farrar, Thomas R. Hawn

Primary Institution: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

Hypothesis

Macrophages from individuals with different clinical manifestations of Mycobacterium tuberculosis infection would have distinct gene expression profiles and that polymorphisms in these genes may also be associated with susceptibility to TB.

Conclusion

The study identified CCL1 as a gene involved in host susceptibility to tuberculosis and demonstrated that genetic variations in this gene are associated with different clinical forms of the disease.

Supporting Evidence

  • 1,608 genes were differentially expressed by greater than 2-fold in Mtb-stimulated macrophages.
  • 90% of the microarray results were confirmed by RT-PCR.
  • Six single nucleotide polymorphisms in CCL1 were found to be associated with TB.

Takeaway

Scientists studied how certain genes in our immune cells respond to tuberculosis and found that some people are more likely to get sick because of their genes.

Methodology

The study measured gene expression levels from ex vivo Mtb-stimulated macrophages in subjects with different clinical phenotypes and confirmed results using real-time PCR.

Potential Biases

Potential selection bias due to the focus on well-characterized genes and the use of a specific Mtb strain.

Limitations

The sample size was small, which may limit the statistical power of the findings.

Participant Demographics

Participants were ethnic Vietnamese Kinh, aged over 14, and HIV-negative.

Statistical Information

P-Value

0.004

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.ppat.1000229

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