Polymorphisms in the Toll-Like Receptor and the IL-23/IL-17 Pathways Were Associated with Susceptibility to Inflammatory Bowel Disease in a Danish Cohort.
BACKGROUND:The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), result from the combined effects of susceptibility genes and environmental factors. Previous studies have shown that polymorphisms in the Toll-like receptor (TLR), the apoptosis, the IL-23/IL-17...
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doaj-6adca32d787e468397931117943be9102020-11-25T01:44:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014530210.1371/journal.pone.0145302Polymorphisms in the Toll-Like Receptor and the IL-23/IL-17 Pathways Were Associated with Susceptibility to Inflammatory Bowel Disease in a Danish Cohort.Steffen BankPaal Skytt AndersenJohan BurischNatalia PedersenStine RougJulied GalsgaardStine Ydegaard TurinoJacob Broder BrodersenShaista RashidBritt Kaiser RasmussenSara AvlundThomas Bastholm OlesenHans Jürgen HoffmannBjørn Andersen NexøJacob SodeUlla VogelVibeke AndersenBACKGROUND:The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), result from the combined effects of susceptibility genes and environmental factors. Previous studies have shown that polymorphisms in the Toll-like receptor (TLR), the apoptosis, the IL-23/IL-17 and the interferon gamma (IFNG) pathways are associated with risk of both CD and UC. METHODS:Using a candidate gene approach, 21 functional single nucleotide polymorphisms (SNPs) in 15 genes were assessed in a clinical homogeneous group of severely diseased ethnic Danish patients consisting of 624 patients with CD, 411 patients with UC and 795 controls. The results were analysed using logistic regression. RESULTS:The polymorphisms TLR5 (rs5744174) and IL12B (rs6887695) were associated with risk of CD, and TLR1 (rs4833095) and IL18 (rs187238) were associated with risk of both CD and UC (p<0.05). After Bonferroni correction for multiple testing, the homozygous variant genotype of TLR1 743 T>C (rs4833095) was associated with increased risk CD (OR: 3.15, 95% CI: 1.59-6.26, p = 0.02) and CD and UC combined (OR: 2.96, 95% CI: 1.64-5.32, p = 0.005). CONCLUSION:Our results suggest that genetically determined high activity of TLR1 and TLR5 was associated with increased risk of both CD and UC and CD, respectively. This supports that the host microbial composition or environmental factors in the gut are involved in risk of IBD. Furthermore, genetically determined high activity of the IL-23/IL-17 pathway was associated with increased risk of CD and UC. Overall, our results support that genetically determined high inflammatory response was associated with increased risk of both CD and UC.http://europepmc.org/articles/PMC4689491?pdf=render |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Steffen Bank Paal Skytt Andersen Johan Burisch Natalia Pedersen Stine Roug Julied Galsgaard Stine Ydegaard Turino Jacob Broder Brodersen Shaista Rashid Britt Kaiser Rasmussen Sara Avlund Thomas Bastholm Olesen Hans Jürgen Hoffmann Bjørn Andersen Nexø Jacob Sode Ulla Vogel Vibeke Andersen |
spellingShingle |
Steffen Bank Paal Skytt Andersen Johan Burisch Natalia Pedersen Stine Roug Julied Galsgaard Stine Ydegaard Turino Jacob Broder Brodersen Shaista Rashid Britt Kaiser Rasmussen Sara Avlund Thomas Bastholm Olesen Hans Jürgen Hoffmann Bjørn Andersen Nexø Jacob Sode Ulla Vogel Vibeke Andersen Polymorphisms in the Toll-Like Receptor and the IL-23/IL-17 Pathways Were Associated with Susceptibility to Inflammatory Bowel Disease in a Danish Cohort. PLoS ONE |
author_facet |
Steffen Bank Paal Skytt Andersen Johan Burisch Natalia Pedersen Stine Roug Julied Galsgaard Stine Ydegaard Turino Jacob Broder Brodersen Shaista Rashid Britt Kaiser Rasmussen Sara Avlund Thomas Bastholm Olesen Hans Jürgen Hoffmann Bjørn Andersen Nexø Jacob Sode Ulla Vogel Vibeke Andersen |
author_sort |
Steffen Bank |
title |
Polymorphisms in the Toll-Like Receptor and the IL-23/IL-17 Pathways Were Associated with Susceptibility to Inflammatory Bowel Disease in a Danish Cohort. |
title_short |
Polymorphisms in the Toll-Like Receptor and the IL-23/IL-17 Pathways Were Associated with Susceptibility to Inflammatory Bowel Disease in a Danish Cohort. |
title_full |
Polymorphisms in the Toll-Like Receptor and the IL-23/IL-17 Pathways Were Associated with Susceptibility to Inflammatory Bowel Disease in a Danish Cohort. |
title_fullStr |
Polymorphisms in the Toll-Like Receptor and the IL-23/IL-17 Pathways Were Associated with Susceptibility to Inflammatory Bowel Disease in a Danish Cohort. |
title_full_unstemmed |
Polymorphisms in the Toll-Like Receptor and the IL-23/IL-17 Pathways Were Associated with Susceptibility to Inflammatory Bowel Disease in a Danish Cohort. |
title_sort |
polymorphisms in the toll-like receptor and the il-23/il-17 pathways were associated with susceptibility to inflammatory bowel disease in a danish cohort. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
BACKGROUND:The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), result from the combined effects of susceptibility genes and environmental factors. Previous studies have shown that polymorphisms in the Toll-like receptor (TLR), the apoptosis, the IL-23/IL-17 and the interferon gamma (IFNG) pathways are associated with risk of both CD and UC. METHODS:Using a candidate gene approach, 21 functional single nucleotide polymorphisms (SNPs) in 15 genes were assessed in a clinical homogeneous group of severely diseased ethnic Danish patients consisting of 624 patients with CD, 411 patients with UC and 795 controls. The results were analysed using logistic regression. RESULTS:The polymorphisms TLR5 (rs5744174) and IL12B (rs6887695) were associated with risk of CD, and TLR1 (rs4833095) and IL18 (rs187238) were associated with risk of both CD and UC (p<0.05). After Bonferroni correction for multiple testing, the homozygous variant genotype of TLR1 743 T>C (rs4833095) was associated with increased risk CD (OR: 3.15, 95% CI: 1.59-6.26, p = 0.02) and CD and UC combined (OR: 2.96, 95% CI: 1.64-5.32, p = 0.005). CONCLUSION:Our results suggest that genetically determined high activity of TLR1 and TLR5 was associated with increased risk of both CD and UC and CD, respectively. This supports that the host microbial composition or environmental factors in the gut are involved in risk of IBD. Furthermore, genetically determined high activity of the IL-23/IL-17 pathway was associated with increased risk of CD and UC. Overall, our results support that genetically determined high inflammatory response was associated with increased risk of both CD and UC. |
url |
http://europepmc.org/articles/PMC4689491?pdf=render |
work_keys_str_mv |
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