Polymorphisms in the NFkB, TNF-alpha, IL-1beta, and IL-18 pathways are associated with response to anti-TNF therapy in Danish patients with inflammatory bowel disease

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Standard

Polymorphisms in the NFkB, TNF-alpha, IL-1beta, and IL-18 pathways are associated with response to anti-TNF therapy in Danish patients with inflammatory bowel disease. / Bank, Steffen; Julsgaard, Mette; Abed, Osama Karim; Burisch, Johan; Brodersen, Jacob Broder; Pedersen, Natalia Konstantinovich; Gouliaev, Anja; Ajan, Rullah; Rasmussen, Ditlev Nytoft; Grauslund, Camilla Honore; Roug, Stine; Galsgaard, Julie; Finsen, David Sprogoe Hoyer; Lindby, Karoline; Sorensen, Jeanette; Larsen, Lone; Andersen, Malene Rohr; Brandslund, Ivan; Thomassen, Mads; Green, Anders; Bojesen, Anders Bo; Sorensen, Signe Bek; Vogel, Ulla; Andersen, Vibeke; Bergmann, Ann Christina; Andersen, Paal Skytt; Rashid, Shaista; Lund, Britta Ornfelt; Rasmussen, Britt Kaiser; Avlund, Sara; Nielsen, Marie Odum; Bramstang, Eva Karolina Nilsdotter; Poulsen, Anja; Rudbeck-Resdal, Ditte; Aamann, Luise; Alexandraki, Maria Joanna; Foroutani, Ali; Molzen, Line; Hatrop, Anders; Rittig, Charlotte Siggaard; Stenbog, Elisabeth; Hedback, Nora Elisabeth; Nielsen, Rasmus Gaardskaer; Schiodt, Frank Vinholt; Carlsen, Katrine; Dessau, Ram Benny; Hoffmann, Hans Jurgen; Nexo, Bjorn Andersen; Sode, Jacob.

I: Alimentary Pharmacology and Therapeutics, Bind 49, Nr. 7, 2019, s. 890-903.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Bank, S, Julsgaard, M, Abed, OK, Burisch, J, Brodersen, JB, Pedersen, NK, Gouliaev, A, Ajan, R, Rasmussen, DN, Grauslund, CH, Roug, S, Galsgaard, J, Finsen, DSH, Lindby, K, Sorensen, J, Larsen, L, Andersen, MR, Brandslund, I, Thomassen, M, Green, A, Bojesen, AB, Sorensen, SB, Vogel, U, Andersen, V, Bergmann, AC, Andersen, PS, Rashid, S, Lund, BO, Rasmussen, BK, Avlund, S, Nielsen, MO, Bramstang, EKN, Poulsen, A, Rudbeck-Resdal, D, Aamann, L, Alexandraki, MJ, Foroutani, A, Molzen, L, Hatrop, A, Rittig, CS, Stenbog, E, Hedback, NE, Nielsen, RG, Schiodt, FV, Carlsen, K, Dessau, RB, Hoffmann, HJ, Nexo, BA & Sode, J 2019, 'Polymorphisms in the NFkB, TNF-alpha, IL-1beta, and IL-18 pathways are associated with response to anti-TNF therapy in Danish patients with inflammatory bowel disease', Alimentary Pharmacology and Therapeutics, bind 49, nr. 7, s. 890-903. https://doi.org/10.1111/apt.15187

APA

Bank, S., Julsgaard, M., Abed, O. K., Burisch, J., Brodersen, J. B., Pedersen, N. K., Gouliaev, A., Ajan, R., Rasmussen, D. N., Grauslund, C. H., Roug, S., Galsgaard, J., Finsen, D. S. H., Lindby, K., Sorensen, J., Larsen, L., Andersen, M. R., Brandslund, I., Thomassen, M., ... Sode, J. (2019). Polymorphisms in the NFkB, TNF-alpha, IL-1beta, and IL-18 pathways are associated with response to anti-TNF therapy in Danish patients with inflammatory bowel disease. Alimentary Pharmacology and Therapeutics, 49(7), 890-903. https://doi.org/10.1111/apt.15187

Vancouver

Bank S, Julsgaard M, Abed OK, Burisch J, Brodersen JB, Pedersen NK o.a. Polymorphisms in the NFkB, TNF-alpha, IL-1beta, and IL-18 pathways are associated with response to anti-TNF therapy in Danish patients with inflammatory bowel disease. Alimentary Pharmacology and Therapeutics. 2019;49(7):890-903. https://doi.org/10.1111/apt.15187

Author

Bank, Steffen ; Julsgaard, Mette ; Abed, Osama Karim ; Burisch, Johan ; Brodersen, Jacob Broder ; Pedersen, Natalia Konstantinovich ; Gouliaev, Anja ; Ajan, Rullah ; Rasmussen, Ditlev Nytoft ; Grauslund, Camilla Honore ; Roug, Stine ; Galsgaard, Julie ; Finsen, David Sprogoe Hoyer ; Lindby, Karoline ; Sorensen, Jeanette ; Larsen, Lone ; Andersen, Malene Rohr ; Brandslund, Ivan ; Thomassen, Mads ; Green, Anders ; Bojesen, Anders Bo ; Sorensen, Signe Bek ; Vogel, Ulla ; Andersen, Vibeke ; Bergmann, Ann Christina ; Andersen, Paal Skytt ; Rashid, Shaista ; Lund, Britta Ornfelt ; Rasmussen, Britt Kaiser ; Avlund, Sara ; Nielsen, Marie Odum ; Bramstang, Eva Karolina Nilsdotter ; Poulsen, Anja ; Rudbeck-Resdal, Ditte ; Aamann, Luise ; Alexandraki, Maria Joanna ; Foroutani, Ali ; Molzen, Line ; Hatrop, Anders ; Rittig, Charlotte Siggaard ; Stenbog, Elisabeth ; Hedback, Nora Elisabeth ; Nielsen, Rasmus Gaardskaer ; Schiodt, Frank Vinholt ; Carlsen, Katrine ; Dessau, Ram Benny ; Hoffmann, Hans Jurgen ; Nexo, Bjorn Andersen ; Sode, Jacob. / Polymorphisms in the NFkB, TNF-alpha, IL-1beta, and IL-18 pathways are associated with response to anti-TNF therapy in Danish patients with inflammatory bowel disease. I: Alimentary Pharmacology and Therapeutics. 2019 ; Bind 49, Nr. 7. s. 890-903.

Bibtex

@article{202c3073dd4848dc8c1cb2d96a5aa9b4,
title = "Polymorphisms in the NFkB, TNF-alpha, IL-1beta, and IL-18 pathways are associated with response to anti-TNF therapy in Danish patients with inflammatory bowel disease",
abstract = "BackgroundAnti‐tumor necrosis factor‐α (TNF‐α) is used for the treatment of severe cases of IBD, including Crohn's disease (CD) and ulcerative colitis (UC). However, one‐third of the patients do not respond to the treatment. We have previously investigated whether single nucleotide polymorphisms (SNPs) in genes involved in inflammation were associated with response to anti‐TNF therapy among patients with CD or UC.AimA new cohort of patients was established for replication of the previous findings and to identify new SNPs associated with anti‐TNF response.MethodsFifty‐three SNPs assessed previously in cohort 1 (482 CD and 256 UC patients) were genotyped in cohort 2 (587 CD and 458 UC patients). The results were analysed using logistic regression (adjusted for age and gender).ResultsTen SNPs were associated with anti‐TNF response either among patients with CD (TNFRSF1A(rs4149570) (OR: 1.92, 95% CI: 1.02‐3.60, P = 0.04), IL18(rs187238) (OR: 1.35, 95% CI: 1.00‐1.82, P = 0.05), and JAK2(rs12343867) (OR: 1.35, 95% CI: 1.02‐1.78, P = 0.03)), UC (TLR2(rs11938228) (OR: 0.55, 95% CI: 0.33‐0.92, P = 0.02), TLR4(rs5030728) (OR: 2.23, 95% CI: 1.24‐4.01, P = 0.01) and (rs1554973) (OR: 0.49, 95% CI: 0.27‐0.90, P = 0.02), NFKBIA(rs696) (OR: 1.45, 95% CI: 1.06‐2.00, P = 0.02), and NLRP3(rs4612666) (OR: 0.63, 95% CI: 0.44‐0.91, P = 0.01)) or in the combined cohort of patient with CD and UC (IBD) (TLR4(rs5030728) (OR: 1.46, 95% CI: 1.01‐2.11, P = 0.04) and (rs1554973)(OR: 0.80, 95% CI: 0.65‐0.98, P = 0.03), NFKBIA(rs696) (OR: 1.25, 95% CI: 1.01‐1.54, P = 0.04), NLRP3(rs4612666) (OR: 0.73, 95% CI: 0.57‐0.95, P = 0.02), IL1RN(rs4251961) (OR: 0.81, 95% CI: 0.66‐1.00, P = 0.05), IL18(rs1946518) (OR: 1.24, 95% CI: 1.01‐1.53, P = 0.04), and JAK2(rs12343867) (OR: 1.24, 95% CI: 1.01‐1.53, P = 0.04)).ConclusionsThe results support that polymorphisms in genes involved in the regulation of the NFκB pathway (TLR2, TLR4, and NFKBIA), the TNF‐α signalling pathway (TNFRSF1A), and other cytokine pathways (NLRP3, IL1RN, IL18, and JAK2) were associated with response to anti‐TNF therapy. Our multi‐SNP model predicted response rate of more than 82% (in 9% of the CD patients) and 75% (in 15% of the UC patients), compared to 71% and 64% in all CD and UC patients, respectively. More studies are warranted to predict response for use in the clinic.",
author = "Steffen Bank and Mette Julsgaard and Abed, {Osama Karim} and Johan Burisch and Brodersen, {Jacob Broder} and Pedersen, {Natalia Konstantinovich} and Anja Gouliaev and Rullah Ajan and Rasmussen, {Ditlev Nytoft} and Grauslund, {Camilla Honore} and Stine Roug and Julie Galsgaard and Finsen, {David Sprogoe Hoyer} and Karoline Lindby and Jeanette Sorensen and Lone Larsen and Andersen, {Malene Rohr} and Ivan Brandslund and Mads Thomassen and Anders Green and Bojesen, {Anders Bo} and Sorensen, {Signe Bek} and Ulla Vogel and Vibeke Andersen and Bergmann, {Ann Christina} and Andersen, {Paal Skytt} and Shaista Rashid and Lund, {Britta Ornfelt} and Rasmussen, {Britt Kaiser} and Sara Avlund and Nielsen, {Marie Odum} and Bramstang, {Eva Karolina Nilsdotter} and Anja Poulsen and Ditte Rudbeck-Resdal and Luise Aamann and Alexandraki, {Maria Joanna} and Ali Foroutani and Line Molzen and Anders Hatrop and Rittig, {Charlotte Siggaard} and Elisabeth Stenbog and Hedback, {Nora Elisabeth} and Nielsen, {Rasmus Gaardskaer} and Schiodt, {Frank Vinholt} and Katrine Carlsen and Dessau, {Ram Benny} and Hoffmann, {Hans Jurgen} and Nexo, {Bjorn Andersen} and Jacob Sode",
year = "2019",
doi = "10.1111/apt.15187",
language = "English",
volume = "49",
pages = "890--903",
journal = "Alimentary Pharmacology and Therapeutics, Supplement",
issn = "0953-0673",
publisher = "Wiley-Blackwell",
number = "7",

}

RIS

TY - JOUR

T1 - Polymorphisms in the NFkB, TNF-alpha, IL-1beta, and IL-18 pathways are associated with response to anti-TNF therapy in Danish patients with inflammatory bowel disease

AU - Bank, Steffen

AU - Julsgaard, Mette

AU - Abed, Osama Karim

AU - Burisch, Johan

AU - Brodersen, Jacob Broder

AU - Pedersen, Natalia Konstantinovich

AU - Gouliaev, Anja

AU - Ajan, Rullah

AU - Rasmussen, Ditlev Nytoft

AU - Grauslund, Camilla Honore

AU - Roug, Stine

AU - Galsgaard, Julie

AU - Finsen, David Sprogoe Hoyer

AU - Lindby, Karoline

AU - Sorensen, Jeanette

AU - Larsen, Lone

AU - Andersen, Malene Rohr

AU - Brandslund, Ivan

AU - Thomassen, Mads

AU - Green, Anders

AU - Bojesen, Anders Bo

AU - Sorensen, Signe Bek

AU - Vogel, Ulla

AU - Andersen, Vibeke

AU - Bergmann, Ann Christina

AU - Andersen, Paal Skytt

AU - Rashid, Shaista

AU - Lund, Britta Ornfelt

AU - Rasmussen, Britt Kaiser

AU - Avlund, Sara

AU - Nielsen, Marie Odum

AU - Bramstang, Eva Karolina Nilsdotter

AU - Poulsen, Anja

AU - Rudbeck-Resdal, Ditte

AU - Aamann, Luise

AU - Alexandraki, Maria Joanna

AU - Foroutani, Ali

AU - Molzen, Line

AU - Hatrop, Anders

AU - Rittig, Charlotte Siggaard

AU - Stenbog, Elisabeth

AU - Hedback, Nora Elisabeth

AU - Nielsen, Rasmus Gaardskaer

AU - Schiodt, Frank Vinholt

AU - Carlsen, Katrine

AU - Dessau, Ram Benny

AU - Hoffmann, Hans Jurgen

AU - Nexo, Bjorn Andersen

AU - Sode, Jacob

PY - 2019

Y1 - 2019

N2 - BackgroundAnti‐tumor necrosis factor‐α (TNF‐α) is used for the treatment of severe cases of IBD, including Crohn's disease (CD) and ulcerative colitis (UC). However, one‐third of the patients do not respond to the treatment. We have previously investigated whether single nucleotide polymorphisms (SNPs) in genes involved in inflammation were associated with response to anti‐TNF therapy among patients with CD or UC.AimA new cohort of patients was established for replication of the previous findings and to identify new SNPs associated with anti‐TNF response.MethodsFifty‐three SNPs assessed previously in cohort 1 (482 CD and 256 UC patients) were genotyped in cohort 2 (587 CD and 458 UC patients). The results were analysed using logistic regression (adjusted for age and gender).ResultsTen SNPs were associated with anti‐TNF response either among patients with CD (TNFRSF1A(rs4149570) (OR: 1.92, 95% CI: 1.02‐3.60, P = 0.04), IL18(rs187238) (OR: 1.35, 95% CI: 1.00‐1.82, P = 0.05), and JAK2(rs12343867) (OR: 1.35, 95% CI: 1.02‐1.78, P = 0.03)), UC (TLR2(rs11938228) (OR: 0.55, 95% CI: 0.33‐0.92, P = 0.02), TLR4(rs5030728) (OR: 2.23, 95% CI: 1.24‐4.01, P = 0.01) and (rs1554973) (OR: 0.49, 95% CI: 0.27‐0.90, P = 0.02), NFKBIA(rs696) (OR: 1.45, 95% CI: 1.06‐2.00, P = 0.02), and NLRP3(rs4612666) (OR: 0.63, 95% CI: 0.44‐0.91, P = 0.01)) or in the combined cohort of patient with CD and UC (IBD) (TLR4(rs5030728) (OR: 1.46, 95% CI: 1.01‐2.11, P = 0.04) and (rs1554973)(OR: 0.80, 95% CI: 0.65‐0.98, P = 0.03), NFKBIA(rs696) (OR: 1.25, 95% CI: 1.01‐1.54, P = 0.04), NLRP3(rs4612666) (OR: 0.73, 95% CI: 0.57‐0.95, P = 0.02), IL1RN(rs4251961) (OR: 0.81, 95% CI: 0.66‐1.00, P = 0.05), IL18(rs1946518) (OR: 1.24, 95% CI: 1.01‐1.53, P = 0.04), and JAK2(rs12343867) (OR: 1.24, 95% CI: 1.01‐1.53, P = 0.04)).ConclusionsThe results support that polymorphisms in genes involved in the regulation of the NFκB pathway (TLR2, TLR4, and NFKBIA), the TNF‐α signalling pathway (TNFRSF1A), and other cytokine pathways (NLRP3, IL1RN, IL18, and JAK2) were associated with response to anti‐TNF therapy. Our multi‐SNP model predicted response rate of more than 82% (in 9% of the CD patients) and 75% (in 15% of the UC patients), compared to 71% and 64% in all CD and UC patients, respectively. More studies are warranted to predict response for use in the clinic.

AB - BackgroundAnti‐tumor necrosis factor‐α (TNF‐α) is used for the treatment of severe cases of IBD, including Crohn's disease (CD) and ulcerative colitis (UC). However, one‐third of the patients do not respond to the treatment. We have previously investigated whether single nucleotide polymorphisms (SNPs) in genes involved in inflammation were associated with response to anti‐TNF therapy among patients with CD or UC.AimA new cohort of patients was established for replication of the previous findings and to identify new SNPs associated with anti‐TNF response.MethodsFifty‐three SNPs assessed previously in cohort 1 (482 CD and 256 UC patients) were genotyped in cohort 2 (587 CD and 458 UC patients). The results were analysed using logistic regression (adjusted for age and gender).ResultsTen SNPs were associated with anti‐TNF response either among patients with CD (TNFRSF1A(rs4149570) (OR: 1.92, 95% CI: 1.02‐3.60, P = 0.04), IL18(rs187238) (OR: 1.35, 95% CI: 1.00‐1.82, P = 0.05), and JAK2(rs12343867) (OR: 1.35, 95% CI: 1.02‐1.78, P = 0.03)), UC (TLR2(rs11938228) (OR: 0.55, 95% CI: 0.33‐0.92, P = 0.02), TLR4(rs5030728) (OR: 2.23, 95% CI: 1.24‐4.01, P = 0.01) and (rs1554973) (OR: 0.49, 95% CI: 0.27‐0.90, P = 0.02), NFKBIA(rs696) (OR: 1.45, 95% CI: 1.06‐2.00, P = 0.02), and NLRP3(rs4612666) (OR: 0.63, 95% CI: 0.44‐0.91, P = 0.01)) or in the combined cohort of patient with CD and UC (IBD) (TLR4(rs5030728) (OR: 1.46, 95% CI: 1.01‐2.11, P = 0.04) and (rs1554973)(OR: 0.80, 95% CI: 0.65‐0.98, P = 0.03), NFKBIA(rs696) (OR: 1.25, 95% CI: 1.01‐1.54, P = 0.04), NLRP3(rs4612666) (OR: 0.73, 95% CI: 0.57‐0.95, P = 0.02), IL1RN(rs4251961) (OR: 0.81, 95% CI: 0.66‐1.00, P = 0.05), IL18(rs1946518) (OR: 1.24, 95% CI: 1.01‐1.53, P = 0.04), and JAK2(rs12343867) (OR: 1.24, 95% CI: 1.01‐1.53, P = 0.04)).ConclusionsThe results support that polymorphisms in genes involved in the regulation of the NFκB pathway (TLR2, TLR4, and NFKBIA), the TNF‐α signalling pathway (TNFRSF1A), and other cytokine pathways (NLRP3, IL1RN, IL18, and JAK2) were associated with response to anti‐TNF therapy. Our multi‐SNP model predicted response rate of more than 82% (in 9% of the CD patients) and 75% (in 15% of the UC patients), compared to 71% and 64% in all CD and UC patients, respectively. More studies are warranted to predict response for use in the clinic.

U2 - 10.1111/apt.15187

DO - 10.1111/apt.15187

M3 - Journal article

C2 - 30811631

VL - 49

SP - 890

EP - 903

JO - Alimentary Pharmacology and Therapeutics, Supplement

JF - Alimentary Pharmacology and Therapeutics, Supplement

SN - 0953-0673

IS - 7

ER -

ID: 228204966