An eQTL variant of ZXDC is associated with IFN-γ production following Mycobacterium tuberculosis antigen-specific stimulation. 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. G., Delacourt, C., Schurr, E., & Abel, L. Scientific Reports, 7(1):12800, October, 2017. doi abstract bibtex 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-ESAT6BCGphenotype and rs9828868 on chromosome 3q (p = 9.8 × 10-6in the French sample). This variant made a significant contribution to the linkage signal (p \textless 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.
@article{jabot-hanin_eqtl_2017,
title = {An {eQTL} variant of {ZXDC} is associated with {IFN}-γ production following {Mycobacterium} tuberculosis antigen-specific stimulation},
volume = {7},
issn = {2045-2322},
doi = {10.1038/s41598-017-13017-8},
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 {\textasciitilde}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-ESAT6BCGphenotype and rs9828868 on chromosome 3q (p = 9.8 × 10-6in the French sample). This variant made a significant contribution to the linkage signal (p {\textless} 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.},
language = {eng},
number = {1},
journal = {Scientific Reports},
author = {Jabot-Hanin, Fabienne and Cobat, Aurélie and Feinberg, Jacqueline and Orlova, Marianna and Niay, Jonathan and Deswarte, Caroline and Poirier, Christine and Theodorou, Ioannis and Bustamante, Jacinta and Boisson-Dupuis, Stéphanie and Casanova, Jean-Laurent and Alcaïs, Alexandre and Hoal, Eileen G. and Delacourt, Christophe and Schurr, Erwin and Abel, Laurent},
month = oct,
year = {2017},
pmid = {28993696},
pmcid = {PMC5634485},
pages = {12800},
}
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G.","Delacourt, C.","Schurr, E.","Abel, L."],"year":2017,"bibtype":"article","biburl":"http://bibbase.org/zotero/TBHostGen","bibdata":{"bibtype":"article","type":"article","title":"An eQTL variant of ZXDC is associated with IFN-γ production following Mycobacterium tuberculosis antigen-specific stimulation","volume":"7","issn":"2045-2322","doi":"10.1038/s41598-017-13017-8","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-ESAT6BCGphenotype and rs9828868 on chromosome 3q (p = 9.8 × 10-6in the French sample). This variant made a significant contribution to the linkage signal (p \\textless 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.","language":"eng","number":"1","journal":"Scientific Reports","author":[{"propositions":[],"lastnames":["Jabot-Hanin"],"firstnames":["Fabienne"],"suffixes":[]},{"propositions":[],"lastnames":["Cobat"],"firstnames":["Aurélie"],"suffixes":[]},{"propositions":[],"lastnames":["Feinberg"],"firstnames":["Jacqueline"],"suffixes":[]},{"propositions":[],"lastnames":["Orlova"],"firstnames":["Marianna"],"suffixes":[]},{"propositions":[],"lastnames":["Niay"],"firstnames":["Jonathan"],"suffixes":[]},{"propositions":[],"lastnames":["Deswarte"],"firstnames":["Caroline"],"suffixes":[]},{"propositions":[],"lastnames":["Poirier"],"firstnames":["Christine"],"suffixes":[]},{"propositions":[],"lastnames":["Theodorou"],"firstnames":["Ioannis"],"suffixes":[]},{"propositions":[],"lastnames":["Bustamante"],"firstnames":["Jacinta"],"suffixes":[]},{"propositions":[],"lastnames":["Boisson-Dupuis"],"firstnames":["Stéphanie"],"suffixes":[]},{"propositions":[],"lastnames":["Casanova"],"firstnames":["Jean-Laurent"],"suffixes":[]},{"propositions":[],"lastnames":["Alcaïs"],"firstnames":["Alexandre"],"suffixes":[]},{"propositions":[],"lastnames":["Hoal"],"firstnames":["Eileen","G."],"suffixes":[]},{"propositions":[],"lastnames":["Delacourt"],"firstnames":["Christophe"],"suffixes":[]},{"propositions":[],"lastnames":["Schurr"],"firstnames":["Erwin"],"suffixes":[]},{"propositions":[],"lastnames":["Abel"],"firstnames":["Laurent"],"suffixes":[]}],"month":"October","year":"2017","pmid":"28993696","pmcid":"PMC5634485","pages":"12800","bibtex":"@article{jabot-hanin_eqtl_2017,\n\ttitle = {An {eQTL} variant of {ZXDC} is associated with {IFN}-γ production following {Mycobacterium} tuberculosis antigen-specific stimulation},\n\tvolume = {7},\n\tissn = {2045-2322},\n\tdoi = {10.1038/s41598-017-13017-8},\n\tabstract = {There is a large inter-individual variability in the response to Mycobacterium tuberculosis infection. 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