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 \textasciitilde100,000 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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