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Identification of tuberculosis susceptibility gene

Globally, nearly one and a half billion people are carriers of Mycobacterium Tuberculosis. Approximately ten percent of such carriers present with clinically manifest tuberculosis due to vulnerability of the immune system to combat the microbe. Untreated, the disease may lead to fatality. For example, during the first half of the 20th century, the leading cause of death in Turkey was tuberculosis. As a result of great efforts by the Ministry of Health, Refik Saydam Hygiene Center and tuberculosis treatment clinics the incidence of the disease decreased significantly. But complete eradication -like in polio or smallpox- has not been possible. Globally, tuberculosis remains the most common communicable disease and among the top ten causes of death. In Turkey, according to the Ministry of Health statistics, there are approximately fifteen thousand cases.

Why tuberculosis remains such a prevalent health burden, despite all these efforts, is a question that the scientific world has been tackling for a long time. One prominent reason is Mendelian susceptibility to mycobacterial disease. In other words, humans carry mutations that make them vulnerable to tuberculosis. The gene mutations that are involved in such a susceptibility began to emerge in the 1990’s but they were all very rare identified in a handful of patients. Now, scientists identified a common mutation that leads to tuberculosis susceptibility. The result is published in Science Immunology (http://immunology.sciencemag.org/content/3/30/eaau8714).

The team, which includes Professor Tayfun Özçelik from Bilkent University and clinicians from United States, Australia, Brazil, Morocco, France, Sweden, Iran, Canada, Singapore, Chile and Turkey, lead by Professor Jean-Laurent Casanova from Rockefeller University, discovered that a common mutation in TYK2 gene leads to tuberculosis susceptibility.

The mutation is frequently seen in the population reaching to levels to become one of the most common forms of autosomal recessive inheritance documented in humans. For example, approximately one in ten individuals in Europe and one twenty individuals in Turkey are heterozygote. This translates to approximately one million Europeans and 80.000 Turks could be homozygotes. Such individuals, if confronted by mycobacterium tuberculosis infection, are highly susceptible to develop clinically manifest tuberculosis in their lungs and/or possibly other organs.

Researchers are now studying the TYK2 gene and interferon signaling pathway to devise strategies for the early detection, carrier screening and treatment of tuberculosis.