C10X polymorphism in the CARD8 gene is associated with bacteraemia

Immunity, Inflammation and Disease

Berhane Asfaw Idosa¹  Berolla Sahdo¹  Ermias Balcha¹  Anne Kelly¹  Bo Söderquist² 

[1] Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden;Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden

关键词: Bacteraemia;    blood culture;    gene variants;    infection;    inflammasomes;    inflammation;    innate immunity;    leukocytes;    polymorphisms;    sepsis;   

DOI  :  10.1002/iid3.14

来源: Wiley

【 摘 要 】

Abstract

The NLRP3 inflammasome is an intracellular multi-protein complex that triggers caspase-1 mediated maturation of interleukin-1β (IL-1β); one of the most potent mediators of inflammation and a major cytokine produced during severe infections, like sepsis. However, the excessive cytokine levels seem to stage for tissue injury and organ failure, and high levels of IL-1β correlates with severity and mortality of sepsis. Instead, recent data suggest caspase-1 to function as a guardian against severe infections. CARD8 has been implied to regulate the synthesis of IL-1β via interaction to caspase-1. In recent years, polymorphism of CARD8 (C10X) per se or in combination with NLRP3 (Q705K) has been implicated with increased risk of inflammation. The aim was to investigate the correlation of these polymorphisms with severe blood stream infection. Human DNA was extracted from blood culture bottles that were found to be positive for microbial growth (i.e. patients with bacteraemia). Polymorphisms Q705K in the NLRP3 gene and C10X in the CARD8 gene were genotyped using TaqMan genotyping assay. The results were compared to healthy controls and to samples from patients with negative cultures. The polymorphism C10X was significantly over-represented among patients with bacteraemia as compared to healthy controls, whereas patients with negative blood culture were not associated with a higher prevalence. No association was observed with polymorphism Q705K of NLRP3 in either group of patients. Patients carrying polymorphism C10X in the CARD8 gene are at increased risk of developing bacteraemia and severe inflammation.

【 授权许可】

CC BY   
© 2013 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

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