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
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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