The Genetic Diversity and Dysfunctionality of Catalase Associated with a Worse Outcome in Crohn's Disease
| Autor: | Marisa Iborra, Inés Moret, Enrique Busó, José Luis García-Giménez, Elena Ricart, Javier P. Gisbert, Eduard Cabré, Maria Esteve, Lucía Márquez-Mosquera, Esther García-Planella, Jordi Guardiola, Federico V. Pallardó, Carolina Serena, Francisco Algaba-Chueca, Eugeni Domenech, Pilar Nos, Belén Beltrán |
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| Rok vydání: | 2022 |
| Předmět: |
Crohn’s disease
Genotype Estrès oxidatiu Polymorphism Single Nucleotide Inflammatory bowel disease Catalysis Antioxidants catalase inflammatory bowel disease oxidative stress antioxidant genes Inorganic Chemistry Malaltia de Crohn Crohn Disease Genetics Humans Genetic Predisposition to Disease Physical and Theoretical Chemistry Molecular Biology Spectroscopy Retrospective Studies Inflammation Organic Chemistry Genetic Variation General Medicine Catalase Computer Science Applications Crohn's disease Oxidative stress Case-Control Studies Antioxidant genes Genètica |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 24; Pages: 15881 |
| ISSN: | 1422-0067 |
| Popis: | 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: | OpenAIRE |
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