The genetic diversity and dysfunctionality of catalase associated with a worse outcome in Crohn's disease

Iborra, Marisa; Moret, Inés; Busó, Enrique; García-Giménez, José Luis; Ricart, Elena; Gisbert, Javier P.; Cabré, Eduard; Esteve, Maria; Márquez-Mosquera, Lucía; García-Planella, Esther; Guardiola, Jordi; Pallardó, Federico V.; Serena, Carolina; Algaba-Chueca, Francisco; Domenech, Eugeni; Nos, Pilar; Beltrán, Belén

The genetic diversity and dysfunctionality of catalase associated with a worse outcome in Crohn's disease

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dc.contributor.author Iborra, Marisa
dc.contributor.author Moret, Inés
dc.contributor.author Busó, Enrique
dc.contributor.author García-Giménez, José Luis
dc.contributor.author Ricart, Elena
dc.contributor.author Gisbert, Javier P.
dc.contributor.author Cabré, Eduard
dc.contributor.author Esteve, Maria
dc.contributor.author Márquez-Mosquera, Lucía
dc.contributor.author García-Planella, Esther
dc.contributor.author Guardiola, Jordi
dc.contributor.author Pallardó, Federico V.
dc.contributor.author Serena, Carolina
dc.contributor.author Algaba-Chueca, Francisco
dc.contributor.author Domenech, Eugeni
dc.contributor.author Nos, Pilar
dc.contributor.author Beltrán, Belén
dc.date.accessioned 2023-04-13T06:23:31Z
dc.date.available 2023-04-13T06:23:31Z
dc.date.issued 2022
dc.description.abstract Chronic gut inflammation in Crohn’s disease (CD) is associated with an increase in oxidative stress and an imbalance of antioxidant enzymes. We have previously shown that catalase (CAT) activity is permanently inhibited by CD. The purpose of the study was to determine whether there is any relationship between the single nucleotide polymorphisms (SNPs) in the CAT enzyme and the potential risk of CD associated with high levels of oxidative stress. Additionally, we used protein and regulation analyses to determine what causes long-term CAT inhibition in peripheral white mononuclear cells (PWMCs) in both active and inactive CD. We first used a retrospective cohort of 598 patients with CD and 625 age-matched healthy controls (ENEIDA registry) for the genotype analysis. A second human cohort was used to study the functional and regulatory mechanisms of CAT in CD. We isolated PWMCs from CD patients at the onset of the disease (naïve CD patients). In the genotype-association SNP analysis, the CAT SNPs rs1001179, rs475043, and rs525938 showed a significant association with CD (p < 0.001). Smoking CD patients with the CAT SNP rs475043 A/G genotype had significantly more often penetrating disease (p = 0.009). The gene expression and protein levels of CAT were permanently reduced in the active and inactive CD patients. The inhibition of CAT activity in the PWMCs of the CD patients was related to a low concentration of CAT protein caused by the downregulation of CAT-gene transcription. Our study suggests an association between CAT SNPs and the risk of CD that may explain permanent CAT inhibition in CD patients together with low CAT gene and protein expression.
dc.format.mimetype application/pdf
dc.identifier.citation Iborra M, Moret I, Busó E, García-Giménez JL, Ricart E, Gisbert JP, Cabré E, Esteve M, Márquez-Mosquera L, García-Planella E, Guardiola J, Pallardó FV, Serena C, Algaba-Chueca F, Domenech E, Nos P, Beltrán B. The genetic diversity and dysfunctionality of catalase associated with a worse outcome in Crohn's disease. Int J Mol Sci. 2022 Dec 14;23(24):15881. DOI: 10.3390/ijms232415881
dc.identifier.doi http://dx.doi.org/10.3390/ijms232415881
dc.identifier.issn 1422-0067
dc.identifier.uri http://hdl.handle.net/10230/56455
dc.language.iso eng
dc.publisher MDPI
dc.relation.ispartof Int J Mol Sci. 2022 Dec 14;23(24):15881
dc.rights © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword Crohn’s disease
dc.subject.keyword Antioxidant genes
dc.subject.keyword Catalase
dc.subject.keyword Inflammatory bowel disease
dc.subject.keyword Oxidative stress
dc.title The genetic diversity and dysfunctionality of catalase associated with a worse outcome in Crohn's disease
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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