News Release

Gene with probable role in human susceptibility to pulmonary tuberculosis identified

Males are more likely to contract the disease

Peer-Reviewed Publication

Agency for Science, Technology and Research (A*STAR), Singapore

A new gene that may confer susceptibility to pulmonary tuberculosis has been identified by Genome Institute of Singapore (GIS) researchers and their collaborators in The Netherlands, Indonesia, United Kingdom, and the Russian Federation.

In the current j PLoS Genetics, the scientists report that the gene, named Toll-like receptor 8 (TLR8), which had been previously shown to recognize some factors from viruses such as the human immunodeficiency virus (HIV), also has a probable role in human susceptibility to Mycobacterium tuberculosis infections.

The study also found that males are more susceptible than females.

"We are really excited about this discovery as it is the first time TLR8 has been implicated in bacteria infections," said Dr. Sonia Davila, GIS Research Scientist and first author of the article.

"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," Dr. Davia added. "These findings open up a whole new area of research and we hope that it will increase our understanding of the disease process of pulmonary tuberculosis."

GIS Senior Group Leader and Associate Director of Infectious Diseases, Dr. Martin Hibberd noted, "This project is a great example of international teams coming together to solve a difficult problem, with groups from Indonesia, Singapore, UK, Russia and the Netherlands playing important roles. We hope that this work can initiate further research that will make a difference to people suffering from TB".

"The team from the Genome Institute led by Drs. Davila, Seielstad and Hibberd has made an important new discovery of an alternative cellular receptor for one of the world's most important infectious agents, M. tuberculosis, the causative agent of TB," said Dr. Paul MacAry, Assistant Professor at National University of Singapore Graduate School for Integrative Sciences and Engineering.

"The identification of a role for TLR8 in TB infection has the potential to open up new areas of exploration in TB host/pathogen interactions and provide researchers and clinician scientists with novel targets for therapeutic intervention," Dr. MacAry added. "This is extremely important given the emergence of multi-drug resistant strains of M.tuberculosis that are refractive to current treatment regimes."

Pulmonary tuberculosis is a contagious lung disease caused by a bacterium known as Mycobacterium tuberculosis (M. tuberculosis). Although a third of the world population is infected with M. tuberculosis, only 5 to 10% of them will ever develop tuberculosis, giving rise to a proposition that there may be a difference in genetic variants within the genes involved in host immune response.–––––––––––––

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The research findings are published in the October 8, 2008 issue of PLoS Genetics in an article titled, "Genetic Association and Expression Studies Indicate a Role of Toll-Like Receptor 8 in Pulmonary Tuberculosis".

Authors:

Sonia Davil (1), Martin L. Hibberd (1), Ranjeeta Hari Dass (1), Hazel E.E. Wong (1), Edhyana Sahiratmadja (3,5), Carine Bonnard (2), Bachti Alisjahbana (6), Jeffrey S Szeszko (7), Yanina Balabanova (8,9), Francis Drobniewski (8), Reinout van Crevel (10), Esther van de Vosse (4), Sergey Nejentsev (7,11), Tom H.M. Ottenhoff (3,4), Mark Seielstad (2).

(1) Infectious Diseases, Genome Institute of Singapore

(2) Human Genetics, Genome Institute of Singapore

(3) Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands

(4) Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands

(5) Eijkman Institute for Molecular Biology, Jakarta, Indonesia

(6) Department of Internal Medicine, Padjadjaran University, Hasan Sadikin Hospital, Bandung, Indonesia

(7) Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, Department of Medical Genetics, University of Cambridge, Cambridge, UK

(8) Health Protection Agency Mycobacterium Reference Unit and Clinical TB and HIV Group, Center for Infectious Diseases, Institute for Cell and Molecular Sciences, Barts and the London Medical School, London, UK

(9) Samara Region Tuberculosis Service, Samara, Russian Federation

(10) Department of Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands

(11) Department of Medicine, University of Cambridge, Cambridge, UK

GENOME INSTITUTE OF SINGAPORE (GIS):
www.gis.a-star.edu.sg

GIS, a member of the Agency for Science, Technology and Research (A*STAR), is a national initiative with a global vision that seeks to use genomic sciences to improve public health and public prosperity. Established in 2001 as a centre for genomic discovery, GIS l pursues the integration of technology, genetics and biology towards the goal of individualized medicine. Key research areas include Systems Biology, Stem Cell & Developmental Biology, Cancer Biology & Pharmacology, Human Genetics, Infectious Diseases, Genomic Technologies, and Computational & Mathematical Biology. The genomics infrastructure at the GIS is utilized to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.

AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH (A*STAR):
www.a-star.edu.sg

A*STAR is Singapore's lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based Singapore. A*STAR actively nurtures public sector research and development in Biomedical Sciences, Physical Sciences and Engineering, with a particular focus on fields essential to Singapore's manufacturing industry and new growth industries. It oversees 14 research institutes and supports extramural research with the universities, hospital research centres and other local and international partners. At the heart of this knowledge intensive work is human capital. Top local and international scientific talent drive knowledge creation at A*STAR research institutes. The agency also sends scholars for undergraduate, graduate and post-doctoral training in the best universities, a reflection of the high priority A*STAR places on nurturing the next generation of scientific talent.

FOR MORE INFORMATION:
Winnie Serah Lim
GIS Corporate Communications
Tel: (65) 6478 8013
(65) 9730 7884
Email: limcp2@gis.a-star.edu.sg


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