SLCO3A1, A novel crohn's disease-associated gene, regulates nf-κB activity and associates with intestinal perforation.

<h4>Background & aims</h4>To date, only one gene (TNFSF15) has been identified and validated as a Crohn's disease (CD)-associated gene in non-Caucasian populations. This study was designed to identify novel CD-associated single nucleotide polymorphisms (SNPs)/genes and to valida...

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Autores principales:	Shu-Chen Wei, Yan-Yin Tan, Meng-Tzu Weng, Liang-Chuan Lai, Jen-Hao Hsiao, Eric Y Chuang, Chia-Tung Shun, Deng-Cheng Wu, Ai-Wen Kao, Chiao-Shung Chuang, Yen-Hsuan Ni, Ming-Jium Shieh, Chien-Chih Tung, Yun Chen, Cheng-Yi Wang, Ramnik J Xavier, Daniel K Podolsky, Jau-Min Wong
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fded8c6310c0420aad119b8554b6b49c
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spelling	oai:doaj.org-article:fded8c6310c0420aad119b8554b6b49c2021-11-18T08:14:59ZSLCO3A1, A novel crohn's disease-associated gene, regulates nf-κB activity and associates with intestinal perforation.1932-620310.1371/journal.pone.0100515https://doaj.org/article/fded8c6310c0420aad119b8554b6b49c2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24945726/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background & aims</h4>To date, only one gene (TNFSF15) has been identified and validated as a Crohn's disease (CD)-associated gene in non-Caucasian populations. This study was designed to identify novel CD-associated single nucleotide polymorphisms (SNPs)/genes and to validate candidate genes using a functional assay.<h4>Methods</h4>SNPs from 16 CD patients and 16 age- and sex-matched control patients were analyzed using Illumina platform analysis. Subsequently, we expanded the study and followed 53 CD patients and 41 control patients by Sequenom MassArray analysis. Quantitative PCR and immunohistochemical staining were performed to assess mRNA and protein expression of the candidate gene on tissue isolated from CD patients. Genotype was correlated with CD phenotypes. Finally, the candidate gene was cloned and its effect on NF-κB activity assessed using a reporter luciferase assay.<h4>Results</h4>SLCO3A1 (rs207959) reached statistical significance in the first-stage analysis (P = 2.3E-02) and was further validated in the second-stage analysis (P = 1.0E-03). Genotype and phenotype analysis showed that the rs207959 (T) allele is a risk allele that alters SLCO3A1 mRNA expression and is associated with intestinal perforation in CD patients. Higher levels of mRNA and protein expression of SLCO3A1 were seen in CD patients compared with the control group. Overexpression of SLCO3A1 induced increased NF-κB activity and increased phosphorylation of P65, ERK, and JNK. Nicotine augmented the activation of NF-κB in the presence of SLCO3A1.<h4>Conclusions</h4>SLCO3A1, a novel CD-associated gene, mediates inflammatory processes in intestinal epithelial cells through NF-κB transcription activation, resulting in a higher incidence of bowel perforation in CD patients.Shu-Chen WeiYan-Yin TanMeng-Tzu WengLiang-Chuan LaiJen-Hao HsiaoEric Y ChuangChia-Tung ShunDeng-Cheng WuAi-Wen KaoChiao-Shung ChuangYen-Hsuan NiMing-Jium ShiehChien-Chih TungYun ChenCheng-Yi WangRamnik J XavierDaniel K PodolskyJau-Min WongPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 6, p e100515 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shu-Chen Wei Yan-Yin Tan Meng-Tzu Weng Liang-Chuan Lai Jen-Hao Hsiao Eric Y Chuang Chia-Tung Shun Deng-Cheng Wu Ai-Wen Kao Chiao-Shung Chuang Yen-Hsuan Ni Ming-Jium Shieh Chien-Chih Tung Yun Chen Cheng-Yi Wang Ramnik J Xavier Daniel K Podolsky Jau-Min Wong SLCO3A1, A novel crohn's disease-associated gene, regulates nf-κB activity and associates with intestinal perforation.
description	<h4>Background & aims</h4>To date, only one gene (TNFSF15) has been identified and validated as a Crohn's disease (CD)-associated gene in non-Caucasian populations. This study was designed to identify novel CD-associated single nucleotide polymorphisms (SNPs)/genes and to validate candidate genes using a functional assay.<h4>Methods</h4>SNPs from 16 CD patients and 16 age- and sex-matched control patients were analyzed using Illumina platform analysis. Subsequently, we expanded the study and followed 53 CD patients and 41 control patients by Sequenom MassArray analysis. Quantitative PCR and immunohistochemical staining were performed to assess mRNA and protein expression of the candidate gene on tissue isolated from CD patients. Genotype was correlated with CD phenotypes. Finally, the candidate gene was cloned and its effect on NF-κB activity assessed using a reporter luciferase assay.<h4>Results</h4>SLCO3A1 (rs207959) reached statistical significance in the first-stage analysis (P = 2.3E-02) and was further validated in the second-stage analysis (P = 1.0E-03). Genotype and phenotype analysis showed that the rs207959 (T) allele is a risk allele that alters SLCO3A1 mRNA expression and is associated with intestinal perforation in CD patients. Higher levels of mRNA and protein expression of SLCO3A1 were seen in CD patients compared with the control group. Overexpression of SLCO3A1 induced increased NF-κB activity and increased phosphorylation of P65, ERK, and JNK. Nicotine augmented the activation of NF-κB in the presence of SLCO3A1.<h4>Conclusions</h4>SLCO3A1, a novel CD-associated gene, mediates inflammatory processes in intestinal epithelial cells through NF-κB transcription activation, resulting in a higher incidence of bowel perforation in CD patients.
format	article
author	Shu-Chen Wei Yan-Yin Tan Meng-Tzu Weng Liang-Chuan Lai Jen-Hao Hsiao Eric Y Chuang Chia-Tung Shun Deng-Cheng Wu Ai-Wen Kao Chiao-Shung Chuang Yen-Hsuan Ni Ming-Jium Shieh Chien-Chih Tung Yun Chen Cheng-Yi Wang Ramnik J Xavier Daniel K Podolsky Jau-Min Wong
author_facet	Shu-Chen Wei Yan-Yin Tan Meng-Tzu Weng Liang-Chuan Lai Jen-Hao Hsiao Eric Y Chuang Chia-Tung Shun Deng-Cheng Wu Ai-Wen Kao Chiao-Shung Chuang Yen-Hsuan Ni Ming-Jium Shieh Chien-Chih Tung Yun Chen Cheng-Yi Wang Ramnik J Xavier Daniel K Podolsky Jau-Min Wong
author_sort	Shu-Chen Wei
title	SLCO3A1, A novel crohn's disease-associated gene, regulates nf-κB activity and associates with intestinal perforation.
title_short	SLCO3A1, A novel crohn's disease-associated gene, regulates nf-κB activity and associates with intestinal perforation.
title_full	SLCO3A1, A novel crohn's disease-associated gene, regulates nf-κB activity and associates with intestinal perforation.
title_fullStr	SLCO3A1, A novel crohn's disease-associated gene, regulates nf-κB activity and associates with intestinal perforation.
title_full_unstemmed	SLCO3A1, A novel crohn's disease-associated gene, regulates nf-κB activity and associates with intestinal perforation.
title_sort	slco3a1, a novel crohn's disease-associated gene, regulates nf-κb activity and associates with intestinal perforation.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/fded8c6310c0420aad119b8554b6b49c
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SLCO3A1, A novel crohn's disease-associated gene, regulates nf-κB activity and associates with intestinal perforation.

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