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An eQTL variant of ZXDC is associated with IFN-γ production following Mycobacterium tuberculosis antigen-specific stimulation

Article scientifique 2017 Anglais

Résumé

Abstract There is a large inter-individual variability in the response to Mycobacterium tuberculosis infection. In previous linkage analyses, we identified a major locus on chromosome region 8q controlling IFN-γ production after stimulation with live BCG (Bacillus Calmette-Guérin), and a second locus on chromosome region 3q affecting IFN-γ production triggered by the 6-kDa early secretory antigen target (ESAT-6), taking into account the IFN-γ production induced by BCG (IFNγ-ESAT6BCG). High-density genotyping and imputation identified ~100,000 variants within each linkage region, which we tested for association with the corresponding IFN-γ phenotype in families from a tuberculosis household contact study in France. Significant associations were replicated in a South African familial sample. The most convincing association observed was that between the IFNγ-ESAT6BCG phenotype and rs9828868 on chromosome 3q (p = 9.8 × 10−6 in the French sample). This variant made a significant contribution to the linkage signal (p < 0.001), and a trend towards the same association was observed in the South African sample. This variant was reported to be an eQTL of the ZXDC gene, biologically linked to monocyte IL-12 production through CCL2/MCP1. The identification of rs9828868 as a genetic driver of IFNγ production in response to mycobacterial antigens provides new insights into human anti-tuberculosis immunity.

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Jabot‐Hanin, F., Cobat, A., Feinberg, J., Orlova, M., Niay, J., Deswarte, C., Poirier, C., Theodorou, I., Bustamante, J., Boisson‐Dupuis, S., Casanova, J., Alcaïs, A., Hoal, E., Delacourt, C., Schurr, E., Abel, L. (2017). An eQTL variant of ZXDC is associated with IFN-γ production following Mycobacterium tuberculosis antigen-specific stimulation. https://doi.org/10.1038/s41598-017-13017-8

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Auteur(s)

Fabienne Jabot‐Hanin Aurélie Cobat Jacqueline Feinberg Marianna Orlova Jonathan Niay Caroline Deswarte Christine Poirier Ioannis Theodorou Jacinta Bustamante Stéphanie Boisson‐Dupuis Jean‐Laurent Casanova Alexandre Alcaïs Eileen G. Hoal Christophe Delacourt Erwin Schurr Laurent Abel

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