9a9147b05b97ce0c2e19ece52a961f73  pmc_9785615.pdf
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d0bdd7b80cda1ddb3f395a4284cb9002485176fa878e5c94711723166b402dd1  pmc_9785615.pdf

Title:          The Genetic Diversity and Dysfunctionality of Catalase Associated with a Worse Outcome in Crohn’s Disease
Subject:        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.
Keywords:       catalase; inflammatory bowel disease; Crohn’s disease; oxidative stress; antioxidant genes
Author:         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 and Belén Beltrán
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      Title: Results 
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        Title: SNPs in the Catalase Gene Are Associated with the Risk of Crohn’s Disease in a Spanish Population 
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       Item: 
        Title: Catalase Expression Is Permanently Inhibited in Crohn’s Disease Patients 
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       Item: 
        Title: Catalase Expression Is Permanently Inhibited in Crohn’s Disease Patients 
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    Title: The Genetic Diversity and Dysfunctionality of Catalase Associated with a Worse Outcome in Crohn’s Disease
    Author: 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 and Belén Beltrán
    Subject: 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.
    Keywords: catalase; inflammatory bowel disease; Crohn’s disease; oxidative stress; antioxidant genes
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