A common variant close to the "tripwire" linker region of NLRP1 contributes to severe COVID-19

Inflamm Res. 2023 Nov;72(10-11):1933-1940. doi: 10.1007/s00011-022-01670-3. Epub 2022 Nov 23.

Abstract

Objective and design: The heterogeneity of response to SARS-CoV-2 infection is directly linked to the individual genetic background. Genetic variants of inflammasome-related genes have been pointed as risk factors for several inflammatory sterile and infectious disease. In the group of inflammasome receptors, NLRP1 stands out as a good novel candidate as severity factor for COVID-19 disease.

Methods: To address this question, we performed an association study of NLRP1, DPP9, CARD8, IL1B, and IL18 single nucleotide variants (SNVs) in a cohort of 945 COVID-19 patients.

Results: The NLRP1 p.Leu155His in the linker region, target of viral protease, was significantly associated to COVID-19 severity, which could contribute to the excessive cytokine release reported in severe cases.

Conclusion: Inflammasome genetic background contributes to individual response to SARS-CoV-2.

Keywords: COVID-19; Inflammasome; NLRP1; SARS-CoV-2; SNV.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • CARD Signaling Adaptor Proteins / genetics
  • COVID-19* / genetics
  • Humans
  • Inflammasomes* / genetics
  • Inflammasomes* / metabolism
  • NLR Proteins / genetics
  • Neoplasm Proteins / genetics
  • SARS-CoV-2 / metabolism

Substances

  • Inflammasomes
  • Adaptor Proteins, Signal Transducing
  • NLR Proteins
  • NLRP1 protein, human
  • CARD8 protein, human
  • Neoplasm Proteins
  • CARD Signaling Adaptor Proteins