Genotype/phenotype analyses for 53 Crohn's disease associated genetic polymorphisms.

<h4>Background & aims</h4>Recent studies reported a role for more than 70 genes or loci in the susceptibility to Crohn's disease (CD). However, the impact of these associations in clinical practice remains to be defined. The aim of the study was to analyse the relationship betwe...

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Autores principales:	Camille Jung, Jean-Frédéric Colombel, Marc Lemann, Laurent Beaugerie, Matthieu Allez, Jacques Cosnes, Gwenola Vernier-Massouille, Jean-Marc Gornet, Jean-Pierre Gendre, Jean-Pierre Cezard, Frank M Ruemmele, Dominique Turck, Françoise Merlin, Habib Zouali, Christian Libersa, Philippe Dieudé, Nadem Soufir, Gilles Thomas, Jean-Pierre Hugot
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/69dd7896e3914e079bc1d872e437b0c7
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spelling	oai:doaj.org-article:69dd7896e3914e079bc1d872e437b0c72021-11-18T08:03:32ZGenotype/phenotype analyses for 53 Crohn's disease associated genetic polymorphisms.1932-620310.1371/journal.pone.0052223https://doaj.org/article/69dd7896e3914e079bc1d872e437b0c72012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23300620/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background & aims</h4>Recent studies reported a role for more than 70 genes or loci in the susceptibility to Crohn's disease (CD). However, the impact of these associations in clinical practice remains to be defined. The aim of the study was to analyse the relationship between genotypes and phenotypes for the main 53 CD-associated polymorphisms.<h4>Method</h4>A cohort of 798 CD patients with a median follow up of 7 years was recruited by tertiary adult and paediatric gastroenterological centres. A detailed phenotypic description of the disease was recorded, including clinical presentation, response to treatments and complications. The participants were genotyped for 53 CD-associated variants previously reported in the literature and correlations with clinical sub-phenotypes were searched for. A replication cohort consisting of 722 CD patients was used to further explore the putative associations.<h4>Results</h4>The NOD2 rare variants were associated with an earlier age at diagnosis (p = 0.0001) and an ileal involvement (OR = 2.25[1.49-3.41] and 2.77 [1.71-4.50] for rs2066844 and rs2066847, respectively). Colonic lesions were positively associated with the risk alleles of IL23R rs11209026 (OR = 2.25 [1.13-4.51]) and 6q21 rs7746082 (OR = 1.60 [1.10-2.34] and negatively associated with the risk alleles of IRGM rs13361189 (OR = 0.29 [0.11-0.74]) and DEFB1 rs11362 (OR = 0.50 [0.30-0.80]). The ATG16L1 and IRGM variants were associated with a non-inflammatory behaviour (OR = 1.75 [1.22-2.53] and OR = 1.50 [1.04-2.16] respectively). However, these associations lost significance after multiple testing corrections. The protective effect of the IRGM risk allele on colonic lesions was the only association replicated in the second cohort (p = 0.03).<h4>Conclusions</h4>It is not recommended to genotype the studied polymorphisms in routine practice.Camille JungJean-Frédéric ColombelMarc LemannLaurent BeaugerieMatthieu AllezJacques CosnesGwenola Vernier-MassouilleJean-Marc GornetJean-Pierre GendreJean-Pierre CezardFrank M RuemmeleDominique TurckFrançoise MerlinHabib ZoualiChristian LibersaPhilippe DieudéNadem SoufirGilles ThomasJean-Pierre HugotPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e52223 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Camille Jung Jean-Frédéric Colombel Marc Lemann Laurent Beaugerie Matthieu Allez Jacques Cosnes Gwenola Vernier-Massouille Jean-Marc Gornet Jean-Pierre Gendre Jean-Pierre Cezard Frank M Ruemmele Dominique Turck Françoise Merlin Habib Zouali Christian Libersa Philippe Dieudé Nadem Soufir Gilles Thomas Jean-Pierre Hugot Genotype/phenotype analyses for 53 Crohn's disease associated genetic polymorphisms.
description	<h4>Background & aims</h4>Recent studies reported a role for more than 70 genes or loci in the susceptibility to Crohn's disease (CD). However, the impact of these associations in clinical practice remains to be defined. The aim of the study was to analyse the relationship between genotypes and phenotypes for the main 53 CD-associated polymorphisms.<h4>Method</h4>A cohort of 798 CD patients with a median follow up of 7 years was recruited by tertiary adult and paediatric gastroenterological centres. A detailed phenotypic description of the disease was recorded, including clinical presentation, response to treatments and complications. The participants were genotyped for 53 CD-associated variants previously reported in the literature and correlations with clinical sub-phenotypes were searched for. A replication cohort consisting of 722 CD patients was used to further explore the putative associations.<h4>Results</h4>The NOD2 rare variants were associated with an earlier age at diagnosis (p = 0.0001) and an ileal involvement (OR = 2.25[1.49-3.41] and 2.77 [1.71-4.50] for rs2066844 and rs2066847, respectively). Colonic lesions were positively associated with the risk alleles of IL23R rs11209026 (OR = 2.25 [1.13-4.51]) and 6q21 rs7746082 (OR = 1.60 [1.10-2.34] and negatively associated with the risk alleles of IRGM rs13361189 (OR = 0.29 [0.11-0.74]) and DEFB1 rs11362 (OR = 0.50 [0.30-0.80]). The ATG16L1 and IRGM variants were associated with a non-inflammatory behaviour (OR = 1.75 [1.22-2.53] and OR = 1.50 [1.04-2.16] respectively). However, these associations lost significance after multiple testing corrections. The protective effect of the IRGM risk allele on colonic lesions was the only association replicated in the second cohort (p = 0.03).<h4>Conclusions</h4>It is not recommended to genotype the studied polymorphisms in routine practice.
format	article
author	Camille Jung Jean-Frédéric Colombel Marc Lemann Laurent Beaugerie Matthieu Allez Jacques Cosnes Gwenola Vernier-Massouille Jean-Marc Gornet Jean-Pierre Gendre Jean-Pierre Cezard Frank M Ruemmele Dominique Turck Françoise Merlin Habib Zouali Christian Libersa Philippe Dieudé Nadem Soufir Gilles Thomas Jean-Pierre Hugot
author_facet	Camille Jung Jean-Frédéric Colombel Marc Lemann Laurent Beaugerie Matthieu Allez Jacques Cosnes Gwenola Vernier-Massouille Jean-Marc Gornet Jean-Pierre Gendre Jean-Pierre Cezard Frank M Ruemmele Dominique Turck Françoise Merlin Habib Zouali Christian Libersa Philippe Dieudé Nadem Soufir Gilles Thomas Jean-Pierre Hugot
author_sort	Camille Jung
title	Genotype/phenotype analyses for 53 Crohn's disease associated genetic polymorphisms.
title_short	Genotype/phenotype analyses for 53 Crohn's disease associated genetic polymorphisms.
title_full	Genotype/phenotype analyses for 53 Crohn's disease associated genetic polymorphisms.
title_fullStr	Genotype/phenotype analyses for 53 Crohn's disease associated genetic polymorphisms.
title_full_unstemmed	Genotype/phenotype analyses for 53 Crohn's disease associated genetic polymorphisms.
title_sort	genotype/phenotype analyses for 53 crohn's disease associated genetic polymorphisms.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/69dd7896e3914e079bc1d872e437b0c7
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Genotype/phenotype analyses for 53 Crohn's disease associated genetic polymorphisms.

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