Hans Jürgen Hoffmann

Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • N D Loft, Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
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  • L Skov, Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
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  • L Iversen
  • R Gniadecki, Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark; and.
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  • T N Dam, Skin Clinic, Nykoebing Falster, Denmark.
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  • I Brandslund, Department of Clinical Immunology and Biochemistry, Lillebaelt Hospital, Vejle, Denmark.
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  • H J Hoffmann
  • M R Andersen, Department of Clinical Biochemistry, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
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  • R B Dessau, Department of Clinical Microbiology , Slagelse Hospital, Slagelse Denmark
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  • A C Bergmann, Focused Research Unit for Molecular Diagnostic and Clinical Research, IRS-Center Soenderjylland, Laboratory Center, Hospital of Southern Jutland, Aabenraa, Denmark.
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  • N M Andersen, Focused Research Unit for Molecular Diagnostic and Clinical Research, IRS-Center Soenderjylland, Laboratory Center, Hospital of Southern Jutland, Aabenraa, Denmark.
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  • P S Andersen, Department of Microbiology and Infection Control, Serum Institute, Copenhagen, Denmark.
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  • S Bank, Focused Research Unit for Molecular Diagnostic and Clinical Research, IRS-Center Soenderjylland, Laboratory Center, Hospital of Southern Jutland, Aabenraa, Denmark.
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  • U Vogel, The National Research Centre for the Working Environment, Copenhagen Denmark.
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  • V Andersen, Focused Research Unit for Molecular Diagnostic and Clinical Research, IRS-Center Soenderjylland, Laboratory Center, Hospital of Southern Jutland, Aabenraa, Denmark., University of Southern Denmark, OPEN Odense Patient data Explorative Network, Odense University Hospital and University of Southern Denmark

Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab, infliximab, etanercept) and anti-interleukin-12/13 (IL12/23; ustekinumab) are essential for treatment of patients with severe psoriasis. However, a significant proportion of the patients do not respond to a specific treatment. Pharmacogenetics might be a way to predict treatment response. Using a candidate gene approach, 62 mainly functional single-nucleotide polymorphisms (SNPs) in 44 different genes were evaluated in 478 Danish patients with psoriasis undergoing 376 series of anti-TNF treatment and 230 series of ustekinumab treatment. Associations between genetic variants and treatment outcomes (drug survival and Psoriasis Area Severity Index reduction) were assessed using logistic regression analyses (crude and adjusted for gender, age, psoriatic arthritis and previous treatment). After correction for multiple testing controlling the false discovery rate, six SNPs (IL1B (rs1143623, rs1143627), LY96 (rs11465996), TLR2 (rs11938228, rs4696480) and TLR9 (rs352139)) were associated with response to anti-TNF treatment and 4 SNPs (IL1B (rs1143623, rs1143627), TIRAP (rs8177374) and TLR5 (rs5744174)) were associated with response to ustekinumab treatment (q<0.20). The results suggest that genetic variants related to increased IL-1β levels may be unfavorable when treating psoriasis with either anti-TNF or ustekinumab, whereas genetic variants related to high interferon-γ levels may be favorable when treating psoriasis with ustekinumab.The Pharmacogenomics Journal advance online publication, 11 July 2017; doi:10.1038/tpj.2017.31.

Original languageEnglish
JournalPharmacogenomics Journal
Volume18
Issue3
Pages (from-to)494-500
Number of pages7
ISSN1470-269X
DOIs
Publication statusPublished - 22 May 2018

    Research areas

  • TOLL-LIKE RECEPTORS, ANTI-TNF-ALPHA, GENE POLYMORPHISMS, CLINICAL-RESPONSE, INTERFERON-GAMMA, VARIANTS AFFECT, USTEKINUMAB, PROMOTER, PREDICTION, ALLELE, Membrane Glycoproteins/genetics, Humans, Middle Aged, Psoriasis/drug therapy, Male, Receptors, Interleukin-1/genetics, Tumor Necrosis Factor-alpha/antagonists & inhibitors, Ustekinumab/administration & dosage, Adalimumab/administration & dosage, Pharmacogenetics/methods, Adult, Female, Infliximab/administration & dosage, Lymphocyte Antigen 96/genetics, Treatment Outcome, Toll-Like Receptor 2/genetics, Toll-Like Receptor 9/genetics, Interleukin-1beta/genetics, Denmark, Polymorphism, Single Nucleotide, Etanercept/administration & dosage

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