Polymorphisms in the inflammatory pathway genes TLR2, TLR4, TLR9, LY96, NFKBIA, NFKB1, TNFA, TNFRSF1A, IL6R, IL10, IL23R, PTPN22, and PPARG are associated with susceptibility of inflammatory bowel disease in a Danish cohort.
<h4>Background</h4>The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), result from the combined effects of susceptibility genes and environmental factors. Polymorphisms in genes regulating inflammation may explain part of the genetic heritage.<...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0098815 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850162926590099456 |
|---|---|
| author | Steffen Bank Paal Skytt Andersen Johan Burisch Natalia Pedersen Stine Roug Julie Galsgaard Stine Ydegaard Turino Jacob Broder Brodersen Shaista Rashid Britt Kaiser Rasmussen Sara Avlund Thomas Bastholm Olesen Hans Jürgen Hoffmann Marianne Kragh Thomsen Vibeke Ostergaard Thomsen Morten Frydenberg Bjørn Andersen Nexø Jacob Sode Ulla Vogel Vibeke Andersen Vibeke Andersen |
| author_facet | Steffen Bank Paal Skytt Andersen Johan Burisch Natalia Pedersen Stine Roug Julie Galsgaard Stine Ydegaard Turino Jacob Broder Brodersen Shaista Rashid Britt Kaiser Rasmussen Sara Avlund Thomas Bastholm Olesen Hans Jürgen Hoffmann Marianne Kragh Thomsen Vibeke Ostergaard Thomsen Morten Frydenberg Bjørn Andersen Nexø Jacob Sode Ulla Vogel Vibeke Andersen Vibeke Andersen |
| author_sort | Steffen Bank |
| collection | DOAJ |
| description | <h4>Background</h4>The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), result from the combined effects of susceptibility genes and environmental factors. Polymorphisms in genes regulating inflammation may explain part of the genetic heritage.<h4>Methods</h4>Using a candidate gene approach, 39 mainly functional single nucleotide polymorphisms (SNPs) in 26 genes regulating inflammation were assessed in a clinical homogeneous group of severely diseased patients consisting of 624 patients with CD, 411 patients with UC and 795 controls. The results were analysed using logistic regression.<h4>Results</h4>Sixteen polymorphisms in 13 genes involved in regulation of inflammation were associated with risk of CD and/or UC (p ≤ 0.05). The polymorphisms TLR2 (rs1816702), NFKB1 (rs28362491), TNFRSF1A (rs4149570), IL6R (rs4537545), IL23R (rs11209026) and PTPN22 (rs2476601) were associated with risk of CD and the polymorphisms TLR2 (rs1816702), TLR4 (rs1554973 and rs12377632), TLR9 (rs352139), LY96 (rs11465996), NFKBIA (rs696), TNFA (rs1800629), TNFRSF1A (rs4149570), IL10 (rs3024505), IL23R (rs11209026), PTPN22 (rs2476601) and PPARG (rs1801282) were associated with risk of UC. When including all patients (IBD) the polymorphisms TLR2 (rs4696480 and rs1816702), TLR4 (rs1554973 and rs12377632), TLR9 (rs187084), TNFRSF1A (rs4149570), IL6R (rs4537545), IL10 (rs3024505), IL23R (rs11209026) and PTPN22 (rs2476601) were associated with risk. After Bonferroni correction for multiple testing, both the homozygous and the heterozygous variant genotypes of IL23R G>A(rs11209026) (OR(CD,adj): 0.38, 95% CI: 0.21-0.67, p = 0.03; OR(IBD,adj) 0.43, 95% CI: 0.28-0.67, p = 0.007) and PTPN22 1858 G>A(rs2476601) (OR(CD,unadj) 0.54, 95% CI: 0.41-0.72, p = 7*10-4; OR(IBD,unadj): 0.61, 95% CI: 0.48-0.77, p = 0.001) were associated with reduced risk of CD.<h4>Conclusion</h4>The biological effects of the studied polymorphisms suggest that genetically determined high inflammatory response was associated with increased risk of CD. The many SNPs found in TLRs suggest that the host microbial composition or environmental factors in the gut are involved in risk of IBD in genetically susceptible individuals. |
| format | Article |
| id | doaj-art-90b9211ce57a4c46811db2be1a3afde9 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-90b9211ce57a4c46811db2be1a3afde92025-08-20T02:22:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0196e9881510.1371/journal.pone.0098815Polymorphisms in the inflammatory pathway genes TLR2, TLR4, TLR9, LY96, NFKBIA, NFKB1, TNFA, TNFRSF1A, IL6R, IL10, IL23R, PTPN22, and PPARG are associated with susceptibility of inflammatory bowel disease in a Danish cohort.Steffen BankPaal Skytt AndersenJohan BurischNatalia PedersenStine RougJulie GalsgaardStine Ydegaard TurinoJacob Broder BrodersenShaista RashidBritt Kaiser RasmussenSara AvlundThomas Bastholm OlesenHans Jürgen HoffmannMarianne Kragh ThomsenVibeke Ostergaard ThomsenMorten FrydenbergBjørn Andersen NexøJacob SodeUlla VogelVibeke AndersenVibeke Andersen<h4>Background</h4>The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), result from the combined effects of susceptibility genes and environmental factors. Polymorphisms in genes regulating inflammation may explain part of the genetic heritage.<h4>Methods</h4>Using a candidate gene approach, 39 mainly functional single nucleotide polymorphisms (SNPs) in 26 genes regulating inflammation were assessed in a clinical homogeneous group of severely diseased patients consisting of 624 patients with CD, 411 patients with UC and 795 controls. The results were analysed using logistic regression.<h4>Results</h4>Sixteen polymorphisms in 13 genes involved in regulation of inflammation were associated with risk of CD and/or UC (p ≤ 0.05). The polymorphisms TLR2 (rs1816702), NFKB1 (rs28362491), TNFRSF1A (rs4149570), IL6R (rs4537545), IL23R (rs11209026) and PTPN22 (rs2476601) were associated with risk of CD and the polymorphisms TLR2 (rs1816702), TLR4 (rs1554973 and rs12377632), TLR9 (rs352139), LY96 (rs11465996), NFKBIA (rs696), TNFA (rs1800629), TNFRSF1A (rs4149570), IL10 (rs3024505), IL23R (rs11209026), PTPN22 (rs2476601) and PPARG (rs1801282) were associated with risk of UC. When including all patients (IBD) the polymorphisms TLR2 (rs4696480 and rs1816702), TLR4 (rs1554973 and rs12377632), TLR9 (rs187084), TNFRSF1A (rs4149570), IL6R (rs4537545), IL10 (rs3024505), IL23R (rs11209026) and PTPN22 (rs2476601) were associated with risk. After Bonferroni correction for multiple testing, both the homozygous and the heterozygous variant genotypes of IL23R G>A(rs11209026) (OR(CD,adj): 0.38, 95% CI: 0.21-0.67, p = 0.03; OR(IBD,adj) 0.43, 95% CI: 0.28-0.67, p = 0.007) and PTPN22 1858 G>A(rs2476601) (OR(CD,unadj) 0.54, 95% CI: 0.41-0.72, p = 7*10-4; OR(IBD,unadj): 0.61, 95% CI: 0.48-0.77, p = 0.001) were associated with reduced risk of CD.<h4>Conclusion</h4>The biological effects of the studied polymorphisms suggest that genetically determined high inflammatory response was associated with increased risk of CD. The many SNPs found in TLRs suggest that the host microbial composition or environmental factors in the gut are involved in risk of IBD in genetically susceptible individuals.https://doi.org/10.1371/journal.pone.0098815 |
| spellingShingle | Steffen Bank Paal Skytt Andersen Johan Burisch Natalia Pedersen Stine Roug Julie Galsgaard Stine Ydegaard Turino Jacob Broder Brodersen Shaista Rashid Britt Kaiser Rasmussen Sara Avlund Thomas Bastholm Olesen Hans Jürgen Hoffmann Marianne Kragh Thomsen Vibeke Ostergaard Thomsen Morten Frydenberg Bjørn Andersen Nexø Jacob Sode Ulla Vogel Vibeke Andersen Vibeke Andersen Polymorphisms in the inflammatory pathway genes TLR2, TLR4, TLR9, LY96, NFKBIA, NFKB1, TNFA, TNFRSF1A, IL6R, IL10, IL23R, PTPN22, and PPARG are associated with susceptibility of inflammatory bowel disease in a Danish cohort. PLoS ONE |
| title | Polymorphisms in the inflammatory pathway genes TLR2, TLR4, TLR9, LY96, NFKBIA, NFKB1, TNFA, TNFRSF1A, IL6R, IL10, IL23R, PTPN22, and PPARG are associated with susceptibility of inflammatory bowel disease in a Danish cohort. |
| title_full | Polymorphisms in the inflammatory pathway genes TLR2, TLR4, TLR9, LY96, NFKBIA, NFKB1, TNFA, TNFRSF1A, IL6R, IL10, IL23R, PTPN22, and PPARG are associated with susceptibility of inflammatory bowel disease in a Danish cohort. |
| title_fullStr | Polymorphisms in the inflammatory pathway genes TLR2, TLR4, TLR9, LY96, NFKBIA, NFKB1, TNFA, TNFRSF1A, IL6R, IL10, IL23R, PTPN22, and PPARG are associated with susceptibility of inflammatory bowel disease in a Danish cohort. |
| title_full_unstemmed | Polymorphisms in the inflammatory pathway genes TLR2, TLR4, TLR9, LY96, NFKBIA, NFKB1, TNFA, TNFRSF1A, IL6R, IL10, IL23R, PTPN22, and PPARG are associated with susceptibility of inflammatory bowel disease in a Danish cohort. |
| title_short | Polymorphisms in the inflammatory pathway genes TLR2, TLR4, TLR9, LY96, NFKBIA, NFKB1, TNFA, TNFRSF1A, IL6R, IL10, IL23R, PTPN22, and PPARG are associated with susceptibility of inflammatory bowel disease in a Danish cohort. |
| title_sort | polymorphisms in the inflammatory pathway genes tlr2 tlr4 tlr9 ly96 nfkbia nfkb1 tnfa tnfrsf1a il6r il10 il23r ptpn22 and pparg are associated with susceptibility of inflammatory bowel disease in a danish cohort |
| url | https://doi.org/10.1371/journal.pone.0098815 |
| work_keys_str_mv | AT steffenbank polymorphismsintheinflammatorypathwaygenestlr2tlr4tlr9ly96nfkbianfkb1tnfatnfrsf1ail6ril10il23rptpn22andppargareassociatedwithsusceptibilityofinflammatoryboweldiseaseinadanishcohort AT paalskyttandersen polymorphismsintheinflammatorypathwaygenestlr2tlr4tlr9ly96nfkbianfkb1tnfatnfrsf1ail6ril10il23rptpn22andppargareassociatedwithsusceptibilityofinflammatoryboweldiseaseinadanishcohort AT johanburisch polymorphismsintheinflammatorypathwaygenestlr2tlr4tlr9ly96nfkbianfkb1tnfatnfrsf1ail6ril10il23rptpn22andppargareassociatedwithsusceptibilityofinflammatoryboweldiseaseinadanishcohort AT nataliapedersen polymorphismsintheinflammatorypathwaygenestlr2tlr4tlr9ly96nfkbianfkb1tnfatnfrsf1ail6ril10il23rptpn22andppargareassociatedwithsusceptibilityofinflammatoryboweldiseaseinadanishcohort AT stineroug polymorphismsintheinflammatorypathwaygenestlr2tlr4tlr9ly96nfkbianfkb1tnfatnfrsf1ail6ril10il23rptpn22andppargareassociatedwithsusceptibilityofinflammatoryboweldiseaseinadanishcohort AT juliegalsgaard polymorphismsintheinflammatorypathwaygenestlr2tlr4tlr9ly96nfkbianfkb1tnfatnfrsf1ail6ril10il23rptpn22andppargareassociatedwithsusceptibilityofinflammatoryboweldiseaseinadanishcohort AT stineydegaardturino polymorphismsintheinflammatorypathwaygenestlr2tlr4tlr9ly96nfkbianfkb1tnfatnfrsf1ail6ril10il23rptpn22andppargareassociatedwithsusceptibilityofinflammatoryboweldiseaseinadanishcohort AT jacobbroderbrodersen polymorphismsintheinflammatorypathwaygenestlr2tlr4tlr9ly96nfkbianfkb1tnfatnfrsf1ail6ril10il23rptpn22andppargareassociatedwithsusceptibilityofinflammatoryboweldiseaseinadanishcohort AT shaistarashid polymorphismsintheinflammatorypathwaygenestlr2tlr4tlr9ly96nfkbianfkb1tnfatnfrsf1ail6ril10il23rptpn22andppargareassociatedwithsusceptibilityofinflammatoryboweldiseaseinadanishcohort AT brittkaiserrasmussen polymorphismsintheinflammatorypathwaygenestlr2tlr4tlr9ly96nfkbianfkb1tnfatnfrsf1ail6ril10il23rptpn22andppargareassociatedwithsusceptibilityofinflammatoryboweldiseaseinadanishcohort AT saraavlund polymorphismsintheinflammatorypathwaygenestlr2tlr4tlr9ly96nfkbianfkb1tnfatnfrsf1ail6ril10il23rptpn22andppargareassociatedwithsusceptibilityofinflammatoryboweldiseaseinadanishcohort AT thomasbastholmolesen polymorphismsintheinflammatorypathwaygenestlr2tlr4tlr9ly96nfkbianfkb1tnfatnfrsf1ail6ril10il23rptpn22andppargareassociatedwithsusceptibilityofinflammatoryboweldiseaseinadanishcohort AT hansjurgenhoffmann polymorphismsintheinflammatorypathwaygenestlr2tlr4tlr9ly96nfkbianfkb1tnfatnfrsf1ail6ril10il23rptpn22andppargareassociatedwithsusceptibilityofinflammatoryboweldiseaseinadanishcohort AT mariannekraghthomsen polymorphismsintheinflammatorypathwaygenestlr2tlr4tlr9ly96nfkbianfkb1tnfatnfrsf1ail6ril10il23rptpn22andppargareassociatedwithsusceptibilityofinflammatoryboweldiseaseinadanishcohort AT vibekeostergaardthomsen polymorphismsintheinflammatorypathwaygenestlr2tlr4tlr9ly96nfkbianfkb1tnfatnfrsf1ail6ril10il23rptpn22andppargareassociatedwithsusceptibilityofinflammatoryboweldiseaseinadanishcohort AT mortenfrydenberg polymorphismsintheinflammatorypathwaygenestlr2tlr4tlr9ly96nfkbianfkb1tnfatnfrsf1ail6ril10il23rptpn22andppargareassociatedwithsusceptibilityofinflammatoryboweldiseaseinadanishcohort AT bjørnandersennexø polymorphismsintheinflammatorypathwaygenestlr2tlr4tlr9ly96nfkbianfkb1tnfatnfrsf1ail6ril10il23rptpn22andppargareassociatedwithsusceptibilityofinflammatoryboweldiseaseinadanishcohort AT jacobsode polymorphismsintheinflammatorypathwaygenestlr2tlr4tlr9ly96nfkbianfkb1tnfatnfrsf1ail6ril10il23rptpn22andppargareassociatedwithsusceptibilityofinflammatoryboweldiseaseinadanishcohort AT ullavogel polymorphismsintheinflammatorypathwaygenestlr2tlr4tlr9ly96nfkbianfkb1tnfatnfrsf1ail6ril10il23rptpn22andppargareassociatedwithsusceptibilityofinflammatoryboweldiseaseinadanishcohort AT vibekeandersen polymorphismsintheinflammatorypathwaygenestlr2tlr4tlr9ly96nfkbianfkb1tnfatnfrsf1ail6ril10il23rptpn22andppargareassociatedwithsusceptibilityofinflammatoryboweldiseaseinadanishcohort AT vibekeandersen polymorphismsintheinflammatorypathwaygenestlr2tlr4tlr9ly96nfkbianfkb1tnfatnfrsf1ail6ril10il23rptpn22andppargareassociatedwithsusceptibilityofinflammatoryboweldiseaseinadanishcohort |