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Researchers in Singapore have identified a gene associated with susceptibility to tuberculosis (TB).

Their results also indicate that males are more susceptible than females.

The research was published this month (10 October) in the open access journal PLoS Genetics.

A third of the global population is infected with Mycobacterium tuberculosis, but only 5–10 per cent of those infected will ever develop TB, suggesting that genetic variation could be involved in host immune response to M. tuberculosis.

To test this, researchers looked for differences in 18 genes between 375 pulmonary TB patients and 387 controls from Indonesia. They found that changes in a gene called TLR8 are related to TB susceptibility in males.

The team looked for these changes in the TLR8 genes of a further 1,837 pulmonary TB patients and 1,779 controls from Russia, and again found evidence of association in males.

The TLR8 gene is on the X chromosome, of which men only have one copy. "Our analysis suggested that susceptibility was attributed to genetic variants of TLR8. Males carrying only one copy of the gene could have a higher chance of suffering from the disease," says lead author Sonia Davila, a research scientist at the Genome Institute of Singapore.

She adds that TLR8 was previously thought to be involved only in response to viruses, and this study is the first time its involvement with a bacterial infection has been discovered.

"The identification of a role for TLR8 in TB infection has the potential to provide researchers and clinician scientists with novel targets for therapeutic intervention," says Paul MacAry, an assistant professor from the National University of Singapore Graduate School.

Davila adds that Indonesians have a similar genetic variation to Chinese people — the world's second largest TB patient group — so it could be expected that the results can be applied to the latter.

But Gao Qian, a senior scientist at Shanghai-based Fudan University, says so far the link between genes and vulnerability to TB has not been determined and more studies are needed.

"Currently, it is more important to offer free drugs to TB patients and design reasonable regimens for treatments," Gao told SciDev.Net.

Link to the full paper in PLoS Genetics


PLoS Genetics doi 10.1371/journal.pgen.1000218 (2008)

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