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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8432186 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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