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An eQTL variant of ZXDC is associated with IFN-γ production following Mycobacterium tuberculosis antigen-specific stimulation.
- Source :
-
Scientific reports [Sci Rep] 2017 Oct 09; Vol. 7 (1), pp. 12800. Date of Electronic Publication: 2017 Oct 09. - Publication Year :
- 2017
-
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-ESAT6 <subscript>BCG</subscript> ). 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-ESAT6 <subscript>BCG</subscript> phenotype and rs9828868 on chromosome 3q (p = 9.8 × 10 <superscript>-6</superscript> 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.
- Subjects :
- Antigens, Bacterial metabolism
Bacterial Proteins metabolism
Chromosomes, Human, Pair 3 genetics
Genetic Association Studies
Humans
Interferon-gamma genetics
Mycobacterium bovis immunology
Mycobacterium tuberculosis immunology
Phenotype
Polymorphism, Single Nucleotide genetics
Antigens, Bacterial immunology
Interferon-gamma biosynthesis
Quantitative Trait Loci genetics
Transcription Factors genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 28993696
- Full Text :
- https://doi.org/10.1038/s41598-017-13017-8