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Crohn’s Disease Susceptibility and Onset Are Strongly Related to Three NOD2 Gene Haplotypes

The genetic background and the determinants influencing the disease form, course, and onset of inflammatory bowel disease (IBD) remain unresolved. We aimed to determine the NOD2 gene haplotypes and their relationship with IBD occurrence, clinical presentation, and onset, analyzing a cohort of 578 pa...

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Autores principales: Kaczmarek-Ryś, Marta, Hryhorowicz, Szymon Tytus, Lis, Emilia, Banasiewicz, Tomasz, Paszkowski, Jacek, Borejsza-Wysocki, Maciej, Walkowiak, Jarosław, Cichy, Wojciech, Krokowicz, Piotr, Czkwianianc, Elżbieta, Hnatyszyn, Andrzej, Krela-Kaźmierczak, Iwona, Dobrowolska, Agnieszka, Słomski, Ryszard, Pławski, Andrzej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432186/
https://www.ncbi.nlm.nih.gov/pubmed/34501225
http://dx.doi.org/10.3390/jcm10173777
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author Kaczmarek-Ryś, Marta
Hryhorowicz, Szymon Tytus
Lis, Emilia
Banasiewicz, Tomasz
Paszkowski, Jacek
Borejsza-Wysocki, Maciej
Walkowiak, Jarosław
Cichy, Wojciech
Krokowicz, Piotr
Czkwianianc, Elżbieta
Hnatyszyn, Andrzej
Krela-Kaźmierczak, Iwona
Dobrowolska, Agnieszka
Słomski, Ryszard
Pławski, Andrzej
author_facet Kaczmarek-Ryś, Marta
Hryhorowicz, Szymon Tytus
Lis, Emilia
Banasiewicz, Tomasz
Paszkowski, Jacek
Borejsza-Wysocki, Maciej
Walkowiak, Jarosław
Cichy, Wojciech
Krokowicz, Piotr
Czkwianianc, Elżbieta
Hnatyszyn, Andrzej
Krela-Kaźmierczak, Iwona
Dobrowolska, Agnieszka
Słomski, Ryszard
Pławski, Andrzej
author_sort Kaczmarek-Ryś, Marta
collection PubMed
description The genetic background and the determinants influencing the disease form, course, and onset of inflammatory bowel disease (IBD) remain unresolved. We aimed to determine the NOD2 gene haplotypes and their relationship with IBD occurrence, clinical presentation, and onset, analyzing a cohort of 578 patients with IBD, including children, and 888 controls. Imaging or endoscopy with a histopathological confirmation was used to diagnose IBD. Genotyping was performed to assess the differences in genotypic and allelic frequencies. Linkage disequilibrium was analyzed, and associations between haplotypes and clinical data were evaluated. We emphasized the prevalence of risk alleles in all analyzed loci in patients with Crohn disease (CD). Interestingly, c.2722G>C and c.3019_3020insC alleles were also overrepresented in ulcerative colitis (UC). T-C-G-C-insC, T-C-G-T-insC, and T-T-G-T-wt haplotypes were correlated with the late-onset form of CD (OR = 23.01, 5.09, and 17.71, respectively), while T-T-G-T-wt and C-C-G-T-wt were prevalent only in CD children (OR = 29.36, and 12.93, respectively; p-value = 0.001). In conclusion, the presence of c.3019_3020insC along with c.802C>T occurred as the most fundamental contributing diplotype in late-onset CD form, while in CD children, the mutual allele in all predisposing haplotypes was the c.2798 + 158T. Identifying the unique, high-impact haplotypes supports further studies of the NOD2 gene, including haplotypic backgrounds.
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spelling pubmed-84321862021-09-11 Crohn’s Disease Susceptibility and Onset Are Strongly Related to Three NOD2 Gene Haplotypes Kaczmarek-Ryś, Marta Hryhorowicz, Szymon Tytus Lis, Emilia Banasiewicz, Tomasz Paszkowski, Jacek Borejsza-Wysocki, Maciej Walkowiak, Jarosław Cichy, Wojciech Krokowicz, Piotr Czkwianianc, Elżbieta Hnatyszyn, Andrzej Krela-Kaźmierczak, Iwona Dobrowolska, Agnieszka Słomski, Ryszard Pławski, Andrzej J Clin Med Article The genetic background and the determinants influencing the disease form, course, and onset of inflammatory bowel disease (IBD) remain unresolved. We aimed to determine the NOD2 gene haplotypes and their relationship with IBD occurrence, clinical presentation, and onset, analyzing a cohort of 578 patients with IBD, including children, and 888 controls. Imaging or endoscopy with a histopathological confirmation was used to diagnose IBD. Genotyping was performed to assess the differences in genotypic and allelic frequencies. Linkage disequilibrium was analyzed, and associations between haplotypes and clinical data were evaluated. We emphasized the prevalence of risk alleles in all analyzed loci in patients with Crohn disease (CD). Interestingly, c.2722G>C and c.3019_3020insC alleles were also overrepresented in ulcerative colitis (UC). T-C-G-C-insC, T-C-G-T-insC, and T-T-G-T-wt haplotypes were correlated with the late-onset form of CD (OR = 23.01, 5.09, and 17.71, respectively), while T-T-G-T-wt and C-C-G-T-wt were prevalent only in CD children (OR = 29.36, and 12.93, respectively; p-value = 0.001). In conclusion, the presence of c.3019_3020insC along with c.802C>T occurred as the most fundamental contributing diplotype in late-onset CD form, while in CD children, the mutual allele in all predisposing haplotypes was the c.2798 + 158T. Identifying the unique, high-impact haplotypes supports further studies of the NOD2 gene, including haplotypic backgrounds. MDPI 2021-08-24 /pmc/articles/PMC8432186/ /pubmed/34501225 http://dx.doi.org/10.3390/jcm10173777 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kaczmarek-Ryś, Marta
Hryhorowicz, Szymon Tytus
Lis, Emilia
Banasiewicz, Tomasz
Paszkowski, Jacek
Borejsza-Wysocki, Maciej
Walkowiak, Jarosław
Cichy, Wojciech
Krokowicz, Piotr
Czkwianianc, Elżbieta
Hnatyszyn, Andrzej
Krela-Kaźmierczak, Iwona
Dobrowolska, Agnieszka
Słomski, Ryszard
Pławski, Andrzej
Crohn’s Disease Susceptibility and Onset Are Strongly Related to Three NOD2 Gene Haplotypes
title Crohn’s Disease Susceptibility and Onset Are Strongly Related to Three NOD2 Gene Haplotypes
title_full Crohn’s Disease Susceptibility and Onset Are Strongly Related to Three NOD2 Gene Haplotypes
title_fullStr Crohn’s Disease Susceptibility and Onset Are Strongly Related to Three NOD2 Gene Haplotypes
title_full_unstemmed Crohn’s Disease Susceptibility and Onset Are Strongly Related to Three NOD2 Gene Haplotypes
title_short Crohn’s Disease Susceptibility and Onset Are Strongly Related to Three NOD2 Gene Haplotypes
title_sort crohn’s disease susceptibility and onset are strongly related to three nod2 gene haplotypes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432186/
https://www.ncbi.nlm.nih.gov/pubmed/34501225
http://dx.doi.org/10.3390/jcm10173777
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