The Genetic Diversity and Dysfunctionality of Catalase Associated with a Worse Outcome in Crohn's Disease.

Autor: Iborra M; Gastroenterology Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain., Moret I; Medical Research Institute Hospital La Fe (IIS La Fe), 46026 Valencia, Spain., Busó E; Central Unit for Research in Medicine (UCIM), Faculty of Medicine and Dentistry, University of Valencia, 46010 Valencia, Spain., García-Giménez JL; INCLIVA Biomedical Research Institute, Spanish Institute of Health Carlos III, Department of Physiology, Faculty of Medicine and Dentistry, University of Valencia, Center for Biomedical Research Network on Rare Diseases (CIBERER), 46010 Valencia, Spain., Ricart E; Inflammatory Bowel Disease Unit, Gastroenterology Department, Hospital Clìnic de Barcelona, CIBEREHD, IDIBAPS, 08036 Barcelona, Spain., Gisbert JP; Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), CIBEREHD, 28006 Madrid, Spain., Cabré E; Gastroenterology Department, Hospital Germans Trias i Pujol, CIBEREHD, 08916 Badalona, Spain., Esteve M; Gastroenterology Department, Hospital Universitari Mutua de Terrassa, CIBEREHD, 08221 Barcelona, Spain., Márquez-Mosquera L; Servei de Digestiu, Hospital del Mar, Barcelona, IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain., García-Planella E; Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain., Guardiola J; Gastroenterology Department, Hospital Universitari de Bellvitge, Hospital de Llobregat-Barcelona, 08901 Barcelona, Spain., Pallardó FV; INCLIVA Biomedical Research Institute, Spanish Institute of Health Carlos III, Department of Physiology, Faculty of Medicine and Dentistry, University of Valencia, Center for Biomedical Research Network on Rare Diseases (CIBERER), 46010 Valencia, Spain., Serena C; Institut d'Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, 43007 Tarragona, Spain., Algaba-Chueca F; Medicine and Surgery Department, University Rovira i Virgili, 43201 Reus, Spain., Domenech E; Gastroenterology Department, Hospital Germans Trias i Pujol, CIBEREHD, 08916 Badalona, Spain., Nos P; Gastroenterology Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain., Beltrán B; Hospital Vithas Virgen del Consuelo, 46007 Valencia, Spain.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Dec 14; Vol. 23 (24). Date of Electronic Publication: 2022 Dec 14.
DOI: 10.3390/ijms232415881
Abstrakt: 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.
Databáze: MEDLINE
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