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No significant impact of IFN-γ pathway gene variants on tuberculosis susceptibility in a West African population
- Source :
- European Journal of Human Genetics. 24:748-755
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- The concept of interferon-γ (IFN-γ) having a central role in cell-mediated immune defence to Mycobacterium tuberculosis has long been proposed. Observations made through early candidate gene studies of constituents of the IFN-γ pathway have identified moderately associated variants associated with resistance or susceptibility to tuberculosis (TB). By analysing 20 major genes whose proteins contribute to IFN-γ signalling we have assessed a large fraction of the variability in genes that might contribute to susceptibility to TB. Genetic variants were identified by sequencing the promoter regions and all exons of IFNG, IFNGR1, IFNGR2, IRF1, IL12A, IL12B, IL12RB1, IL12RB2, IL23A, IL23R, IL27, EBI3, IL27RA, IL6ST, SOCS1, STAT1, STAT4, JAK2, TYK2 and TBX21 in 69 DNA samples from Ghana. In addition, we screened all exons of IFNGR1 in a Ghanaian study group comprising 1999 TB cases and 2589 controls by high-resolution melting point analysis. The fine-mapping approach allows for a detailed screening of all variants, common and rare. Statistical comparisons of cases and controls, however, did not yield significant results after correction for multiple testing with any of the 246 variants selected for genotyping in this investigation. Gene-wise haplotype tests and analysis of rare variants did not reveal any significant association with susceptibility to TB in our investigation as well. Although this analysis was applied on a plausible set of IFN-γ pathway genes in the largest African TB cohort available so far, the lack of significant results challenges the view that genetic marker of the IFN-γ pathway have an important impact on susceptibility to TB.
- Subjects :
- 0301 basic medicine
Candidate gene
Tuberculosis
Population
Biology
Ghana
Polymorphism, Single Nucleotide
Article
Mycobacterium tuberculosis
Interferon-gamma
03 medical and health sciences
Genetics
medicine
Humans
Promoter Regions, Genetic
education
Gene
Genotyping
Genetics (clinical)
Receptors, Interferon
education.field_of_study
Interleukins
Haplotype
Exons
medicine.disease
biology.organism_classification
STAT Transcription Factors
030104 developmental biology
Genetic Loci
Genetic marker
Case-Control Studies
Subjects
Details
- ISSN :
- 14765438 and 10184813
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- European Journal of Human Genetics
- Accession number :
- edsair.doi.dedup.....f8e54eb127bd06598f56320490e6310d