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Polymorphisms in CARD8 and NLRP3 are associated with extrapulmonary TB and poor clinical outcome in active TB in Ethiopia.
- Source :
-
Scientific reports [Sci Rep] 2019 Feb 28; Vol. 9 (1), pp. 3126. Date of Electronic Publication: 2019 Feb 28. - Publication Year :
- 2019
-
Abstract
- Innate immunity is a first line defense against Mycobacterium tuberculosis infection where inflammasome activation and secretion of the pro-inflammatory cytokine IL-1beta, plays a major role. Thus, genetic polymorphisms in innate immunity-related genes such as CARD8 and NLRP3 may contribute to the understanding of why most exposed individuals do not develop infection. Our aim was to investigate the association between polymorphisms in CARD8 and NLRP3 and active tuberculosis (TB) as well as their relationship to treatment outcome in a high-endemic setting for TB. Polymorphisms in CARD8 (C10X) and NLRP3 (Q705K) were analysed in 1190 TB patients and 1990 healthy donors (HD). There was a significant association between homozygotes in the CARD8 polymorphism and extrapulmonary TB (EPTB), which was not the case for pulmonary TB or HDs. Among TB-patients, there was an association between poor treatment outcome and the NLRP3 (Q705K) polymorphism. Our study shows that inflammasome polymorphisms are associated with EPTB and poor clinical outcome in active TB in Ethiopia. The practical implications and determining causal relationships on a mechanistic level needs further study.
- Subjects :
- Adult
Ethiopia epidemiology
Female
Gene Frequency
Genetic Predisposition to Disease
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Prognosis
Treatment Outcome
Tuberculosis diagnosis
Tuberculosis epidemiology
Tuberculosis therapy
Young Adult
CARD Signaling Adaptor Proteins genetics
NLR Family, Pyrin Domain-Containing 3 Protein genetics
Neoplasm Proteins genetics
Tuberculosis genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 30816317
- Full Text :
- https://doi.org/10.1038/s41598-019-40121-8