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

May 17, 2023

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

Publicated to:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 23 (24): - 2022-12-01 23(24), DOI: 10.3390/ijms232415881

Authors: Iborra, Marisa; Moret, Ines; Buso, Enrique; Luis Garcia-Gimenez, Jose; Ricart, Elena; Gisbert, Javier P.; Cabre, Eduard; Esteve, Maria; Marquez-Mosquera, Lucia; Garcia-Planella, Esther; Guardiola, Jordi; Pallardo, Federico, V; Serena, Carolina; Algaba-Chueca, Francisco; Domenech, Eugeni; Nos, Pilar; Beltran, Belen;

Affiliations

Hosp Badalona Germans Trias & Pujol, Gastroenterol Dept, CIBEREHD, Badalona 08916, Spain - Author

Hosp Clin Barcelona, Gastroenterol Dept, Inflammatory Bowel Dis Unit, IDIBAPS,CIBEREHD, Barcelona 08036, Spain - Author

Hosp La Santa Creu & St Pau, Gastroenterol Dept, Barcelona 08025, Spain - Author

Hosp Mar, IMIM Hosp Mar Med Res Inst, Serv Digestiu, Barcelona 08003, Spain - Author

Hosp Univ Bellvitge, Gastroenterol Dept, Barcelona 08901, Spain - Author

Hosp Univ Joan XXIII, Inst Invest Sanitaria Pere Virgili, Tarragona 43007, Spain - Author

Hosp Univ Mutua Terrassa, Gastroenterol Dept, CIBEREHD, Barcelona 08221, Spain - Author

Hosp Vithas Virgen del Consuelo, Valencia 46007, Spain - Author

La Fe Univ & Polytech Hosp, Gastroenterol Dept, Valencia 46026, Spain - Author

Med Res Inst Hosp La Fe IIS La Fe, Valencia 46026, Spain - Author

Univ Autonoma Madrid UAM, Hosp Univ La Princesa, Inst Invest Sanitaria Princesa IIS Princesa, Gastroenterol Dept,CIBEREHD, Madrid 28006, Spain - Author

Univ Rovira & Virgili, Med & Surg Dept, Reus 43201, Spain - Author

Univ Valencia, Fac Med & Dent, Cent Unit Res Med UCIM, Valencia 46010, Spain - Author

Univ Valencia, Fac Med & Dent, Ctr Biomed Res Network Rare Dis CIBERER,Dept Phys, INCLIVA Biomed Res Inst,Spanish Inst Hlth Carlos, Valencia 46010, Spain - Author

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.

Keywords

antioxidant genescatalasecrohn’s diseaseinflammatory bowel diseaseAntioxidant enzymesAntioxidant genesCatCatalaseCrohn's diseaseCrohn’s diseaseEpidermal-growth-factorInflammatory bowel diseaseInflammatory-bowel-diseaseOxidative stressPromoter polymorphismProtein phosphatase 2aRiskSuperoxide-dismutaseTnf-alpha

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Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position 66/285, thus managing to position itself as a Q1 (Primer Cuartil), in the category Biochemistry & Molecular Biology.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations from Scopus Elsevier, it yields a value for the Field-Weighted Citation Impact from the Scopus agency: 1.03, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

Field Citation Ratio (FCR) from Dimensions: 2.37 (source consulted: Dimensions Aug 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-08-07, the following number of citations:

WoS: 1
Scopus: 6

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

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Abstract

Keywords

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

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