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Philos Trans R Soc Lond B Biol Sci. 2014 May 12;369(1645):20130428. doi: 10.1098/rstb.2013.0428. Print 2014.

Human genetics of tuberculosis: a long and winding road.

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Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, , 75015 Paris, France.


Only a small fraction of individuals exposed to Mycobacterium tuberculosis develop clinical tuberculosis (TB). Over the past century, epidemiological studies have shown that human genetic factors contribute significantly to this interindividual variability, and molecular progress has been made over the past decade for at least two of the three key TB-related phenotypes: (i) a major locus controlling resistance to infection with M. tuberculosis has been identified, and (ii) proof of principle that severe TB of childhood can result from single-gene inborn errors of interferon-γ immunity has been provided; genetic association studies with pulmonary TB in adulthood have met with more limited success. Future genetic studies of these three phenotypes could consider subgroups of subjects defined on the basis of individual (e.g. age at TB onset) or environmental (e.g. pathogen strain) factors. Progress may also be facilitated by further methodological advances in human genetics. Identification of the human genetic variants controlling the various stages and forms of TB is critical for understanding TB pathogenesis. These findings should have major implications for TB control, in the definition of improved prevention strategies, the optimization of vaccines and clinical trials and the development of novel treatments aiming to restore deficient immune responses.


Mendelian predisposition; complex genetic predisposition; genetic variant; latent tuberculosis infection; primary tuberculosis; pulmonary tuberculosis

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