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
Autor: | Shaista Rashid, Morten Frydenberg, Marianne Kragh Thomsen, Vibeke Østergaard Thomsen, Hans Jürgen Hoffmann, Natalia Pedersen, Jacob Sode, Britt Kaiser Rasmussen, Johan Burisch, Julie Galsgaard, Vibeke Andersen, Stine Ydegaard Turino, Paal Skytt Andersen, Steffen Bank, Ulla Vogel, Bjørn A. Nexø, Stine Roug, Thomas Bastholm Olesen, Sara Avlund, Jacob Broder Brodersen |
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Rok vydání: | 2014 |
Předmět: |
Male
Candidate gene lcsh:Medicine Crohn's Disease Artificial Gene Amplification and Extension Inflammatory bowel disease Polymerase Chain Reaction Medicine and Health Sciences lcsh:Science Crohn's disease Multidisciplinary Toll-Like Receptors NF-kappa B Middle Aged Colitis Ulcerative colitis Research Design Female Research Article Adult Immunology Single-nucleotide polymorphism Gastroenterology and Hepatology Biology Research and Analysis Methods Polymorphism Single Nucleotide Autoimmune Diseases PTPN22 medicine Humans Ulcerative Colitis Molecular Biology Techniques Molecular Biology Aged Evolutionary Biology Interleukins Haplotype lcsh:R Inflammatory Bowel Disease Case-control study Biology and Life Sciences Protein Tyrosine Phosphatase Non-Receptor Type 22 medicine.disease Inflammatory Bowel Diseases PPAR gamma Case-Control Studies Genetic Polymorphism lcsh:Q Clinical Immunology Clinical Medicine Population Genetics |
Zdroj: | PLoS ONE PLoS ONE, Vol 9, Iss 6, p e98815 (2014) Bank, S, Skytt Andersen, P, Burisch, J, Pedersen, N, Roug, S, Galsgaard, J, Ydegaard Turino, S, Broder Brodersen, J, Rashid, S, Kaiser Rasmussen, B, Avlund, S, Bastholm Olesen, T, Jürgen Hoffmann, H, Kragh Thomsen, M, Ostergaard Thomsen, V, Frydenberg, M, Andersen Nexø, B, Sode, J, Vogel, U & Andersen, V 2014, ' 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, vol. 9, no. 6, e98815 . https://doi.org/10.1371/journal.pone.0098815 Bank, S, Skytt Andersen, P, Burisch, J, Pedersen, N, Roug, S, Galsgaard, J, Ydegaard Turino, S, Broder Brodersen, J, Rashid, S, Kaiser Rasmussen, B, Avlund, S, Bastholm Olesen, T, Jürgen Hoffmann, H, Kragh Thomsen, M, Ostergaard Thomsen, V, Frydenberg, M, Andersen Nexø, B, Sode, J, Vogel, U & Andersen, V 2014, ' 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, vol. 9, no. 6, pp. e98815 . https://doi.org/10.1371/journal.pone.0098815 |
ISSN: | 1932-6203 |
Popis: | 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. Polymorphisms in genes regulating inflammation may explain part of the genetic heritage.METHODS: 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.RESULTS: 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.CONCLUSION: 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. |
Databáze: | OpenAIRE |
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