Polymorphisms in CARD8 and NLRP3 are associated with extrapulmonary TB and poor clinical outcome in active TB in Ethiopia

Scientific Reports
Ebba AbateThomas Schön

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.

References

May 16, 2009·Annals of the Rheumatic Diseases·Alf KastbomSolbritt Rantapää-Dahlqvist
Apr 25, 2012·Cellular Microbiology·Diane HoubenPeter J Peters
Mar 23, 2013·Annual Review of Immunology·Anne O'GarraMatthew P R Berry
Apr 23, 2014·Immunology·Ayesha J VerrallReimout van Crevel
Apr 17, 2015·Immunological Reviews·Si Ming Man, Thirumala-Devi Kanneganti
Apr 23, 2016·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·D Souza de LimaA Pontillo

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Citations

Apr 4, 2020·Current Pharmaceutical Design·Rita Del PintoDavide Grassi
Apr 20, 2021·Frontiers in Immunology·Mariana Brasil de Andrade FigueiraAya Sadahiro
Apr 14, 2021·American Journal of Respiratory Cell and Molecular Biology·Andrew D GrausteinMary J Emond

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Methods Mentioned

BETA
genotyping

Software Mentioned

Statistica
STATA

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