Academic Journal
The genetic diversity and dysfunctionality of catalase associated with a worse outcome in crohn’s disease
| العنوان: | The genetic diversity and dysfunctionality of catalase associated with a worse outcome in crohn’s disease |
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| المؤلفون: | Iborra, Marisa, Moret, Inés, Busó, Enrique, García-Giménez, José Luis, Ricart, Elena, Pérez Gisbert, Francisco Javier, Cabré, 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 |
| المساهمون: | UAM. Departamento de Medicina |
| بيانات النشر: | MDPI |
| سنة النشر: | 2024 |
| المجموعة: | Universidad Autónoma de Madrid (UAM): Biblos-e Archivo |
| مصطلحات موضوعية: | antioxidant genes, catalase, Crohn’s disease, inflammatory bowel disease, oxidative stress, Medicina |
| الوصف: | 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 ; This research has been funded by grants from the Asociacion Española de Gastroenterología (AEG), Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU), Instituto de Salud Carlos III (FIS PS09/01827 and PI14/01702) |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | International Journal of Molecular Sciences; https://doi.org/10.3390/ijms232415881; Gobierno de España. PI14/01702; International Journal of Molecular Sciences 23.24 (2022): 15881; 1661-6596 (print); 1422-0067 (online); http://hdl.handle.net/10486/710996; 15881-1; 24; 15881-15; 23 |
| DOI: | 10.3390/ijms232415881 |
| الاتاحة: | http://hdl.handle.net/10486/710996 https://doi.org/10.3390/ijms232415881 |
| Rights: | © 2022 by the authors ; Reconocimiento ; openAccess |
| رقم الانضمام: | edsbas.166CE30A |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/ijms232415881 |
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