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Long-Term Follow-Up, Association between CARD15/NOD2 Polymorphisms, and Clinical Disease Behavior in Crohn's Disease Surgical Patients

BACKGROUND: CARD15/NOD2 is the most significant genetic susceptibility in Crohn's disease (CD) even though a relationship between the different polymorphisms and clinical phenotype has not been described yet. The study is aimed at analyzing, in a group of CD patients undergoing surgery, the rel...

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Autores principales: Giudici, Francesco, Cavalli, Tiziana, Luceri, Cristina, Russo, Edda, Zambonin, Daniela, Scaringi, Stefano, Ficari, Ferdinando, Fazi, Marilena, Amedei, Amedeo, Tonelli, Francesco, Malentacchi, Cecilia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932801/
https://www.ncbi.nlm.nih.gov/pubmed/33708009
http://dx.doi.org/10.1155/2021/8854916
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author Giudici, Francesco
Cavalli, Tiziana
Luceri, Cristina
Russo, Edda
Zambonin, Daniela
Scaringi, Stefano
Ficari, Ferdinando
Fazi, Marilena
Amedei, Amedeo
Tonelli, Francesco
Malentacchi, Cecilia
author_facet Giudici, Francesco
Cavalli, Tiziana
Luceri, Cristina
Russo, Edda
Zambonin, Daniela
Scaringi, Stefano
Ficari, Ferdinando
Fazi, Marilena
Amedei, Amedeo
Tonelli, Francesco
Malentacchi, Cecilia
author_sort Giudici, Francesco
collection PubMed
description BACKGROUND: CARD15/NOD2 is the most significant genetic susceptibility in Crohn's disease (CD) even though a relationship between the different polymorphisms and clinical phenotype has not been described yet. The study is aimed at analyzing, in a group of CD patients undergoing surgery, the relationship between CARD15/NOD2 polymorphisms and the clinical CD behavior after a long-term follow-up, in order to identify potential clinical biomarkers of prognosis. METHODS: 191 surgical CD patients were prospectively characterized both for the main single nucleotide polymorphisms of CARD15/NOD2 and for many other environmental risk factors connected with the severe disease form. After a mean follow-up of 7.3 years, the correlations between clinical features and CD natural history were analyzed. RESULTS: CARD15/NOD2 polymorphisms were significantly associated with younger age at diagnosis compared to wild type cases (p < 0.05). Moreover, patients carrying a 3020insC polymorphism presented a larger Δ between diagnosis and surgery (p = 0.0344). Patients carrying an hz881 and a 3020insC exhibited, respectively, a lower rate of responsiveness to azathioprine (p = 0.012), but no difference was found in biologic therapy. Finally, the risk of surgical recurrence was significantly associated, respectively, to age at diagnosis, to familial CD history, to diagnostic delay, to arthritis, and to the presence of perioperative complications. CONCLUSIONS: 3020insC CARD15 polymorphism is associated with an earlier CD onset, and age at CD diagnosis < 27 years was confirmed to have a detrimental effect on its clinical course. In addition, the familiarity seems to be connected with a more aggressive postoperative course. Finally, for the first time, we have observed a lower rate of responsiveness to azathioprine in patients carrying an hz881 and a 3020insC.
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spelling pubmed-79328012021-03-10 Long-Term Follow-Up, Association between CARD15/NOD2 Polymorphisms, and Clinical Disease Behavior in Crohn's Disease Surgical Patients Giudici, Francesco Cavalli, Tiziana Luceri, Cristina Russo, Edda Zambonin, Daniela Scaringi, Stefano Ficari, Ferdinando Fazi, Marilena Amedei, Amedeo Tonelli, Francesco Malentacchi, Cecilia Mediators Inflamm Research Article BACKGROUND: CARD15/NOD2 is the most significant genetic susceptibility in Crohn's disease (CD) even though a relationship between the different polymorphisms and clinical phenotype has not been described yet. The study is aimed at analyzing, in a group of CD patients undergoing surgery, the relationship between CARD15/NOD2 polymorphisms and the clinical CD behavior after a long-term follow-up, in order to identify potential clinical biomarkers of prognosis. METHODS: 191 surgical CD patients were prospectively characterized both for the main single nucleotide polymorphisms of CARD15/NOD2 and for many other environmental risk factors connected with the severe disease form. After a mean follow-up of 7.3 years, the correlations between clinical features and CD natural history were analyzed. RESULTS: CARD15/NOD2 polymorphisms were significantly associated with younger age at diagnosis compared to wild type cases (p < 0.05). Moreover, patients carrying a 3020insC polymorphism presented a larger Δ between diagnosis and surgery (p = 0.0344). Patients carrying an hz881 and a 3020insC exhibited, respectively, a lower rate of responsiveness to azathioprine (p = 0.012), but no difference was found in biologic therapy. Finally, the risk of surgical recurrence was significantly associated, respectively, to age at diagnosis, to familial CD history, to diagnostic delay, to arthritis, and to the presence of perioperative complications. CONCLUSIONS: 3020insC CARD15 polymorphism is associated with an earlier CD onset, and age at CD diagnosis < 27 years was confirmed to have a detrimental effect on its clinical course. In addition, the familiarity seems to be connected with a more aggressive postoperative course. Finally, for the first time, we have observed a lower rate of responsiveness to azathioprine in patients carrying an hz881 and a 3020insC. Hindawi 2021-02-24 /pmc/articles/PMC7932801/ /pubmed/33708009 http://dx.doi.org/10.1155/2021/8854916 Text en Copyright © 2021 Francesco Giudici et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Giudici, Francesco
Cavalli, Tiziana
Luceri, Cristina
Russo, Edda
Zambonin, Daniela
Scaringi, Stefano
Ficari, Ferdinando
Fazi, Marilena
Amedei, Amedeo
Tonelli, Francesco
Malentacchi, Cecilia
Long-Term Follow-Up, Association between CARD15/NOD2 Polymorphisms, and Clinical Disease Behavior in Crohn's Disease Surgical Patients
title Long-Term Follow-Up, Association between CARD15/NOD2 Polymorphisms, and Clinical Disease Behavior in Crohn's Disease Surgical Patients
title_full Long-Term Follow-Up, Association between CARD15/NOD2 Polymorphisms, and Clinical Disease Behavior in Crohn's Disease Surgical Patients
title_fullStr Long-Term Follow-Up, Association between CARD15/NOD2 Polymorphisms, and Clinical Disease Behavior in Crohn's Disease Surgical Patients
title_full_unstemmed Long-Term Follow-Up, Association between CARD15/NOD2 Polymorphisms, and Clinical Disease Behavior in Crohn's Disease Surgical Patients
title_short Long-Term Follow-Up, Association between CARD15/NOD2 Polymorphisms, and Clinical Disease Behavior in Crohn's Disease Surgical Patients
title_sort long-term follow-up, association between card15/nod2 polymorphisms, and clinical disease behavior in crohn's disease surgical patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932801/
https://www.ncbi.nlm.nih.gov/pubmed/33708009
http://dx.doi.org/10.1155/2021/8854916
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