The role of human host genetics in tuberculosis resistance

ABSTRACT

Introduction: Tuberculosis (TB) remains a public health problem: the latest estimate of new incident cases per year is a staggering 10.4 million. Despite this overwhelming number, the majority of the immunocompetent population can control infection with Mycobacterium tuberculosis. The human genome underlies the immune response and contributes to the outcome of TB infection.

Areas covered: Investigations of TB resistance in the general population have closely mirrored those of other infectious diseases and initially involved epidemiological observations. Linkage and association studies, including studies of VDR, SLC11A1 and HLA-DRB1 followed. Genome-wide association studies of common variants, not necessarily sufficient for disease, became possible after technological advancements. Other approaches involved the identification of those individuals with rare disease-causing mutations that strongly predispose to TB, epistasis and the role of ethnicity in disease. Despite these efforts, infection outcome, on an individual basis, cannot yet be predicted.

Expert commentary: The early identification of future disease progressors is necessary to stem the TB epidemic. Human genetics may contribute to this endeavour and could in future suggest pathways to target for disease prevention. This will however require concerted efforts to establish large, well-phenotyped cohorts from different ethnicities, improved genomic resources and a better understanding of the human genome architecture.

KEYWORDS:

• Tuberculosis
• host genetics
• susceptibility
• resistance
• association
• linkage
• GWAS

Declaration of interest

All authors are supported by the South African Medical Research Council. The content is solely the responsibility of the authors and does not necessarily represent the official views of the South African Medical Research Council. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

The Research reported in this publication was supported by the South African Medical Research Council.