Genetically determined high activity of IL-12 and IL-18 in ulcerative colitis and TLR5 in Crohns disease were associated with non-response to anti-TNF therapy

Autor: Paal Skytt Andersen, Steffen Bank, Hans Jürgen Hoffmann, Natalia Pedersen, Johan Burisch, Jacob Sode, Stine Roug, Vibeke Andersen, Stine Ydegaard Turino, Ulla Vogel, Britt Kaiser Rasmussen, Sara Avlund, Julie Galsgaard, Shaista Rashid, Bjørn A. Nexø, Jacob Broder Brodersen, Thomas Bastholm Olesen
Rok vydání: 2016
Předmět:
0301 basic medicine
TBX21
Male
Candidate gene
Disease
Pharmacology
Gastroenterology
Cohort Studies
Crohn Disease
Interferon gamma
Child
Aged
80 and over
Interleukin-18
Middle Aged
Interleukin-12/genetics
Polymorphism
Single Nucleotide/genetics
Ulcerative colitis
Interleukin-12
Molecular Medicine
Interleukin 18
Female
medicine.drug
Adult
medicine.medical_specialty
Adolescent
Toll-Like Receptor 5/genetics
Single-nucleotide polymorphism
Biology
Polymorphism
Single Nucleotide
03 medical and health sciences
Interferon-gamma
Young Adult
Internal medicine
Inflammatory Bowel Diseases/drug therapy
Genetics
medicine
Humans
Interleukin-18/genetics
Aged
Interferon-gamma/genetics
Crohn Disease/genetics
Tumor Necrosis Factor-alpha/antagonists & inhibitors
Tumor Necrosis Factor-alpha
medicine.disease
Inflammatory Bowel Diseases
Toll-Like Receptor 5
030104 developmental biology
TLR5
Colitis
Ulcerative
Colitis
Ulcerative/drug therapy
Zdroj: Bank, S, Andersen, P S, Burisch, J, Pedersen, N, Roug, S, Galsgaard, J, Turino, S Y, Brodersen, J B, Rashid, S, Rasmussen, B K, Avlund, S, Olesen, T B, Hoffmann, H J, Nexø, B A, Sode, J, Vogel, U & Andersen, V 2018, ' Genetically determined high activity of IL-12 and IL-18 in ulcerative colitis and TLR5 in Crohns disease were associated with non-response to anti-TNF therapy ', Pharmacogenomics Journal, vol. 18, no. 1, pp. 87-97 . https://doi.org/10.1038/tpj.2016.84
Bank, S, Andersen, P S, Burisch, J, Pedersen, N, Roug, S, Galsgaard, J, Turino, S Y, Brodersen, J B, Rashid, S, Rasmussen, B K, Avlund, S, Olesen, T B, Hoffmann, H J, Nexø, B A, Sode, J, Vogel, U & Andersen, V 2018, ' Genetically determined high activity of IL-12 and IL-18 in ulcerative colitis and TLR5 in Crohns disease were associated with non-response to anti-TNF therapy ', The Pharmacogenomics Journal, vol. 18, no. 1, pp. 87–97 . https://doi.org/10.1038/tpj.2016.84
ISSN: 1473-1150
Popis: Anti-tumour necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. A recent study indicated that genetically determined high activity of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6 and interferon gamma (IFN-' 3), are associated with non-response to anti-TNF therapy. Using a candidate gene approach, 21 functional single-nucleotide polymorphisms (SNPs) in 14 genes in the Toll-like receptors, the inflammasome and the IFNG pathways were assessed in 482 and 256 prior anti-TNF naïve Danish patients with CD and UC, respectively. The results were analysed using logistic regression (adjusted for age and gender). Eight functional SNPs were associated with anti-TNF response either among patients with CD (TLR5 (rs5744174) and IFNGR2 (rs8126756)), UC (IL12B (rs3212217), IL18 (rs1946518), IFNGR1 (rs2234711), TBX21 (rs17250932) and JAK2 (rs12343867)) or in the combined cohort of patient with CD and UC (IBD) (NLRP3 (rs10754558), IL12B (rs3212217) and IFNGR1 (rs2234711)) (P
Databáze: OpenAIRE
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