TLR8 gene located on X chromosome was implicated, thus making males more likely to contract the disease, according to PLoS Genetics paper.

Scientists have discovered that the toll-like receptor 8 (TLR8) gene may increase susceptibility to pulmonary tuberculosis (TB). They also found that males are more vulnerable than females to Mycobacterium tuberculosis infections.

TLR8 was previously shown only to recognize some factors from viruses such as HIV. “We are really excited about this discovery as it is the first time TLR8 has been implicated in bacteria infections,” says Sonia Davila, Ph.D., research scientist at the Genome Institute of Singapore (GIS). “Our analysis of the results from cohort studies in Indonesia and Russia suggested that susceptibility was attributed to genetic variants of TLR8, which is located at the X chromosome. Males carrying only one copy of the gene could have a higher chance of suffering from the disease.”

The researchers were studying TB association with the expression of 18 genes involved in the toll-like receptor (TLR) pathways. Initially, they genotyped 149 sequence polymorphisms in 375 pulmonary TB patients and 387 controls from Indonesia. They found that four polymorphisms in the TLR8 gene on chromosome X showed evidence of association with TB susceptibility in males, including a nonsynonymous polymorphism rs3764880.

The team then genotyped those four TLR8 polymorphisms in an independent collection of 1,837 pulmonary TB patients and 1,779 controls from Russia. Once again they found evidence of association for rs3764880 in males.

Additionally, a quantitative PCR analysis indicated that TLR8 transcript levels are significantly up-regulated in patients during the acute phase of disease relative to baseline levels following successful chemotherapy. A marked increase in TLR8 protein expression was also observed directly in differentiated macrophages upon infection with M. bovis bacille Calmette-Guérin.

Research on this study, published October 10 in PloS Genetics, was conducted by investigators at the Genome Institute of Singapore and collaborators in The Netherlands, Indonesia, U.K., and the Russian Federation.

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