Physicians' Academy for Cardiovascular Education

Effect of genetically driven NLRP3 inflammasome activation on risk of CAD and CV mortality

News - June 8, 2020

Life-long genetically driven NLRP3 inflammasome activation associated with mortality: A genetic association study of >500,000 individuals

Presented at ERA-EDTA during the virtual meeting by Stefan Schunk (Homburg/Saar, Germany)

Introduction and methods

Inflammation plays a role in the development of CKD and CKD-associated CVD. The active NLRP3 inflammasome cleaves pro-cytokines into their biological active secreted form and is an important player of the innate immune system. The NLRP3 inflammasome can be activated by endogenous mediators such as lipoproteins. It has been recently shown that ApoC3 activates human monocytes, leading to NLRP3 inflammasome activation and systemic inflammation. In humanized mice, ApoC3 induces kidney injury and promotes CKD-associated CVD. The aim of the study was to explore the effect of life-long genetically driven NLRP3 inflammasome activation on the risk of coronary artery disease (CAD) and CV mortality.

The NLRP3 gene locus was screened for single nucleotide polymorphisms (SNPs) with a plausible biological function. Functional validation of the rs10754555 NLRP3 variant was investigated in isolated human monocytes. Furthermore, the association between the rs10754555 NLRP3 variant and the risk of CAD and mortality was investigated in 3,061 patients undergoing coronary angiography who were enrolled in the LURIC study. Findings on the association of the rs10754555 NLRP3 variant with mortality was validated in 489,258 participants of the UK Biobank study (general population) and in 39,755 participants from eight independent studies (CV risk populations).

Main results


The rs10754555 NLRP3 variant was associated with higher C-reactive protein and serum amyloid A plasma levels, which indicate that this SNP is associated with increased systemic inflammation. Homozygous rs10754555 NLRP3 carriers had a significantly higher risk of CV mortality, compared with non-carriers.

- Our reporting is based on the information provided at the ERA-EDTA congress -

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