Past, present and future directions in human genetic susceptibility to tuberculosis

Authors

  • Marlo Möller,

    1. Molecular Biology and Human Genetics, MRC Centre for Molecular and Cellular Biology and the DST/NRF Centre for Biomedical TB Research, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa
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  • Erika De Wit,

    1. Molecular Biology and Human Genetics, MRC Centre for Molecular and Cellular Biology and the DST/NRF Centre for Biomedical TB Research, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa
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  • Eileen G. Hoal

    1. Molecular Biology and Human Genetics, MRC Centre for Molecular and Cellular Biology and the DST/NRF Centre for Biomedical TB Research, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa
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  • Editor: Monique Capron

Correspondence: Eileen G. Hoal, Molecular Biology and Human Genetics, MRC Centre for Molecular and Cellular Biology and the DST/NRF Centre for Biomedical TB Research, Faculty of Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg 7505, South Africa. Tel.: +27 21 938 9412; fax: +27 21 938 9476; e-mail: egvh@sun.ac.za

Abstract

The historical impression that tuberculosis was an inherited disorder has come full circle and substantial evidence now exists of the human genetic contribution to susceptibility to tuberculosis. This evidence has come from several whole-genome linkage scans, and numerous case-control association studies where the candidate genes were derived from the genome screens, animal models and hypotheses pertaining to the disease pathways. Although many of the associated genes have not been validated in all studies, the list of those that have been is growing, and includes NRAMP1, IFNG, NOS2A, MBL, VDR and some TLR. Certain of these genes have consistently been associated with tuberculosis in diverse populations. The future investigation of susceptibility to tuberculosis is almost certain to include genome-wide association studies, admixture mapping and the search for rare variants and epigenetic mechanisms. The genetic identification of more vulnerable individuals is expected to inform personalized treatment and perhaps vaccination strategies.

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