Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis.
| Title: | Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis. |
|---|---|
| Authors: | Loft ND; Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.; Skov L; Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.; Iversen L; Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.; Gniadecki R; Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark.; Dam TN; Skin Clinic, Nykoebing Falster, Denmark.; Brandslund I; Department of Clinical Immunology and Biochemistry, Lillebaelt Hospital, Vejle, Denmark.; Hoffmann HJ; Institute of Clinical Medicine, Aarhus University, and Department of Respiratory Diseases and Allergy B, Aarhus University Hospital, Aarhus, Denmark.; Andersen MR; Department of Clinical Biochemistry, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.; Dessau RB; Department of Clinical Microbiology, Slagelse Hospital, Slagelse, Denmark.; Bergmann AC; Focused Research Unit for Molecular Diagnostic and Clinical Research, IRS-Center Soenderjylland, Laboratory Center, Hospital of Southern Jutland, Aabenraa, Denmark.; Andersen NM; Focused Research Unit for Molecular Diagnostic and Clinical Research, IRS-Center Soenderjylland, Laboratory Center, Hospital of Southern Jutland, Aabenraa, Denmark.; Andersen PS; Department of Microbiology and Infection Control, Serum Institute, Copenhagen, Denmark.; Bank S; Focused Research Unit for Molecular Diagnostic and Clinical Research, IRS-Center Soenderjylland, Laboratory Center, Hospital of Southern Jutland, Aabenraa, Denmark.; Vogel U; National Research Centre for the Working Environment, Copenhagen, Denmark.; Andersen V; Focused Research Unit for Molecular Diagnostic and Clinical Research, IRS-Center Soenderjylland, Laboratory Center, Hospital of Southern Jutland, Aabenraa, Denmark.; Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.; OPEN (Odense Patient data Explorative Network), University of Southern Denmark, Odense, Denmark. |
| Source: | The pharmacogenomics journal [Pharmacogenomics J] 2018 May 22; Vol. 18 (3), pp. 494-500. Date of Electronic Publication: 2017 Jul 11. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101083949 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1473-1150 (Electronic) Linking ISSN: 1470269X NLM ISO Abbreviation: Pharmacogenomics J Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Avenet, NJ : Nature Pub. Group, c2001- |
| MeSH Terms: | Pharmacogenetics/*methods ; Psoriasis/*drug therapy ; Psoriasis/*genetics; Adalimumab/administration & dosage ; Adalimumab/adverse effects ; Etanercept/administration & dosage ; Etanercept/adverse effects ; Infliximab/administration & dosage ; Infliximab/adverse effects ; Interleukin-1beta/genetics ; Lymphocyte Antigen 96/genetics ; Membrane Glycoproteins/genetics ; Psoriasis/epidemiology ; Psoriasis/pathology ; Receptors, Interleukin-1/genetics ; Toll-Like Receptor 2/genetics ; Toll-Like Receptor 9/genetics ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Ustekinumab/administration & dosage ; Ustekinumab/adverse effects ; Adult ; Denmark ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Treatment Outcome |
| Abstract: | 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 |
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| Substance Nomenclature: | 0 (IL1B protein, human); 0 (Interleukin-1beta); 0 (LY96 protein, human); 0 (Lymphocyte Antigen 96); 0 (Membrane Glycoproteins); 0 (Receptors, Interleukin-1); 0 (TIRAP protein, human); 0 (TLR2 protein, human); 0 (TLR9 protein, human); 0 (Toll-Like Receptor 2); 0 (Toll-Like Receptor 9); 0 (Tumor Necrosis Factor-alpha); B72HH48FLU (Infliximab); FU77B4U5Z0 (Ustekinumab); FYS6T7F842 (Adalimumab); OP401G7OJC (Etanercept) |
| Entry Date(s): | Date Created: 20170712 Date Completed: 20190111 Latest Revision: 20190111 |
| Update Code: | 20260130 |
| DOI: | 10.1038/tpj.2017.31 |
| PMID: | 28696418 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't