An international research team that includes Prof. Tayfun Özçelik, dean of the Faculty of Science and a member of the Department of Molecular Biology and Genetics, has recently published its identification of a common genetic mutation that leads to tuberculosis susceptibility. This discovery has potentially significant implications for humankind, not least due to the scale of the problem of tuberculosis infection.
Globally, nearly one and a half billion people are carriers of Mycobacterium tuberculosis, the bacterium that causes this disease in humans. Approximately 10 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, the Refik Saydam Hygiene Center and tuberculosis treatment clinics, the incidence of the disease decreased significantly. But complete eradication – as has been accomplished in this country and many others in the case of polio and smallpox – has not been possible. Worldwide, tuberculosis remains the most common communicable disease and among the top 10 causes of death. In Turkey, according to Ministry of Health statistics, there are approximately 15,000 cases.
Why tuberculosis remains such a prevalent health burden, despite all the efforts to combat it, is a question that the scientific world has been looking at 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 involved in this susceptibility began to be pinpointed in the 1990s, but they were all very rare, identified in only a handful of patients. Now, scientists have identified a common mutation that leads to tuberculosis susceptibility. The result was published in the December 2018 issue of Science Immunology (http://immunology.sciencemag.org/content/3/30/eaau8714).
The team – which includes, along with Prof. Özçelik, clinicians from the United States, Australia, Brazil, Morocco, France, Sweden, Iran, Canada, Singapore, Chile and Turkey led by Prof. Jean-Laurent Casanova of Rockefeller University – discovered that a common mutation in the TYK2 gene leads to tuberculosis susceptibility.
The mutation is frequently seen in the human population, reaching to levels such that it is one of the most common forms of autosomal recessive inheritance documented in humans. For example, approximately 1 in 10 individuals in Europe and 1 in 20 individuals in Turkey are heterozygotes – meaning that approximately one million
Europeans and 80,000 Turks could be homozygotes. Such individuals, if confronted by Mycobacterium tuberculosis infection, are highly susceptible to developing 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.