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

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

Vinicius N C Leal  1 , Leandro M Paulino  2 , Raylane A G Cambui  1 , Thiago G Zupelli  1 , Suemy M Yamada  1 , Leonardo A T Oliveira  1 , Valéria de F Dutra  3 , Carolina B Bub  3 , Araci M Sakashita  3 , Ana Paula H Yokoyama  3 , José M Kutner  3 , Camila A Vieira  2 , Wellyngton M de S Santiago  2 , Milena M S Andrade  4 , Franciane M E Teixeira  4 , Ricardo W Alberca  4 , Sarah C Gozzi-Silva  4 , Tatiana M Yendo  5 , Lucas C Netto  6 , Alberto J S Duarte  4   7 , Maria N Sato  4 , James Venturini  2 , Alessandra Pontillo  8
Affiliations

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

Vinicius N C Leal et al. Inflamm Res. 2023 Nov.

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Schematic representation of NLRP1 and CARD8 inflammasomes
See this image and copyright information in PMC

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