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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

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

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. More... »

PAGES

12800

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-017-13017-8

DOI

http://dx.doi.org/10.1038/s41598-017-13017-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1092092370

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28993696


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