Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/192506
Title: | The Genetic Diversity and Dysfunctionality of Catalase Associated with a Worse Outcome in Crohn’s Disease |
Author: | Iborra, Marisa Moret, Inés Busó, Enrique García Giménez, José Luis Ricart, Elena Gisbert, J. P. Cabré i Gelada, Eduard Esteve, Maria Márquez Mosquera, Lucía García Planella, Esther Guardiola, Jordi Pallardó, Federico V. Serena, Carolina Algaba Chueca, Francisco Domènech, Eugeni Nos, Pilar Beltrán, Belén |
Keywords: | Malaltia de Crohn Estrès oxidatiu Antioxidants Genètica Crohn's disease Oxidative stress Antioxidants Genetics |
Issue Date: | 14-Dec-2022 |
Publisher: | MDPI AG |
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 (naive 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.3390/ijms232415881 |
It is part of: | International Journal of Molecular Sciences, 2022, vol. 23, num. 24, p. 15881 |
URI: | http://hdl.handle.net/2445/192506 |
Related resource: | https://doi.org/10.3390/ijms232415881 |
ISSN: | 1422-0067 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
ijms-23-15881.pdf | 702.89 kB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License