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      Genetic polymorphisms associated with psoriasis and development of psoriatic arthritis in patients with psoriasis

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          Abstract

          Background

          Psoriasis (PsO) is a chronic inflammatory disease with predominantly cutaneous manifestations. Approximately one third of patients with PsO develop psoriatic arthritis (PsA), whereas the remaining proportion of patients has isolated cutaneous psoriasis (PsC). These two phenotypes share common immunology, but with different heredity that might in part be explained by genetic variables.

          Methods

          Using a candidate gene approach, we studied 53 single nucleotide polymorphisms (SNPs) in 37 genes that regulate inflammation. In total, we assessed 480 patients with PsO from DERMBIO, of whom 151 had PsC for 10 years or more (PsC10), 459 patients with PsA from DANBIO, and 795 healthy controls. Using logistic regression analysis, crude and adjusted for age and gender, we assessed associations between genetic variants and PsO, PsC10, and PsA, as well as associations between genetic variants and development of PsA in PsO.

          Results

          Eleven polymorphisms in 10 genes were nominally associated with PsO and/or PsC and/or PsA ( P < 0.05). After correction for multiple testing with a false discovery rate of 5%, two SNPs remained significant: TNF (rs361525) was associated with PsO, PsC10, and PsA; and IL12B (rs6887695) was associated with PsO.

          Conclusion

          Among a cohort of Danish patients with moderate-to-severe psoriasis, two SNPs in the IL12B and TNF genes were associated with susceptibility of psoriasis. None of the SNPs were specifically associated with isolated cutaneous psoriasis or psoriatic arthritis.

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          Most cited references55

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Psoriatic arthritis: epidemiology, clinical features, course, and outcome.

            Psoriatic arthritis (PsA) has been defined as a unique inflammatory arthritis associated with psoriasis. Its exact prevalence is unknown, but estimates vary from 0.3% to 1% of the population. The clinical features described initially are recognised by most experienced clinicians, although they are most distinct in early disease. Initially, PsA typically presents as an oligoarticular and mild disease. However, with time PsA becomes polyarticular, and it is a severe disease in at least 20% of patients. Patients with PsA who present with polyarticular disease are at risk for disease progression. In addition to progression of clinical and radiological damage, health related quality of life is reduced among patients with PsA. It important to note that patients included in recent drug trials resemble patients followed prospectively in a clinic.
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              Diagnostic delay of more than 6 months contributes to poor radiographic and functional outcome in psoriatic arthritis.

              (1) To investigate the demographic and clinical characteristics contributing to the delay from symptom onset to the first visit to a rheumatologist; (2) to compare clinical, radiographic and patient-reported outcome measures of those who saw a rheumatologist early in their disease course with those who were diagnosed later.
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: ResourcesRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: Data curationRole: ResourcesRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                1 February 2018
                2018
                : 13
                : 2
                : e0192010
                Affiliations
                [1 ] Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
                [2 ] Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark
                [3 ] Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark
                [4 ] Dermatology Clinic, Nykoebing Falster, Denmark
                [5 ] Department of Clinical Immunology and Biochemistry, Lillebaelt Hospital, Vejle, Denmark
                [6 ] Institute of Clinical Medicine, Aarhus University, and Department of Respiratory Diseases and Allergy B, Aarhus University Hospital, Aarhus, Denmark
                [7 ] Department of Clinical Biochemistry, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
                [8 ] Department of Clinical Microbiology, Slagelse Hospital, Slagelse, Denmark
                [9 ] Focused research unit for Molecular Diagnostic and Clinical Research, IRS-Center Soenderjylland, Hospital of Southern Jutland, Aabenraa, Denmark
                [10 ] Zitelab Aps, Copenhagen, Denmark
                [11 ] Department of Microbiology and Infection Control, Serum Institute, Copenhagen, Denmark
                [12 ] Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
                [13 ] The DANBIO registry and Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre of Head and Orthopaedics, Rigshospitalet, Glostrup, Denmark
                [14 ] Department of Rheumatology, Herlev and Gentofte Hospital, Hellerup, Denmark
                [15 ] National Research Centre for the Working Environment, Copenhagen, Denmark
                [16 ] Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
                [17 ] OPEN (Odense Patient data Explorative Network), University of Southern Denmark, Odense, Denmark
                Universita degli Studi di Roma Tor Vergata, ITALY
                Author notes

                Competing Interests: Dr. Skov has received consultancy and/or speaker honoraria from Abbvie, Pfizer, Janssen-Cilag, Merck Sharp & Dohme (MSD), and LEO Pharma and is a member of the advisory boards of Abbvie, Pfizer, Janssen-Cilag, MSD, Eli Lilly, Celgene, and Novartis. Dr. Rasmussen has been a paid speaker for Pfizer, AbbVie, Eli Lilly, and LEO Pharma. He has been consulting or serving on expert/advisory boards with Abbvie, Janssen-Cilag, Novartis, and Eli Lilly. He has served as investigator for Eli Lilly. Dr. Gniadecki has received consultancy and speaker honoraria from Abbvie, Janssen-Cilag, and Novartis and is a member of the advisory boards of Abbvie, Amgen, Janssen-Cilag, Eli Lilly, Celgen, Novartis, and Therakos. Dr. Dam has received compensation as a speaker and member of an advisory board for Janssen-Cilag and Abbvie. Dr. Vibeke Andersen has received compensation as a consultant and member of an advisory board for MSD and Janssen-Cilag. Dr. Glintborg has received research grants from Biogen and Abbvie. Dr. Hetland is a member of the advisory board of Celltrion and has received compensation as a speaker for Roche, Pfizer, and Biogen. MKA is employed by Zitelap Aps, which is responsible for management of the DERMBIO and DANBIO databases. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0002-2950-3280
                Article
                PONE-D-17-38089
                10.1371/journal.pone.0192010
                5794107
                29389950
                2be0b0ad-ce16-4503-8b9a-5096ac0cf78f
                © 2018 Loft et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 25 October 2017
                : 14 January 2018
                Page count
                Figures: 0, Tables: 3, Pages: 12
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100000329, Novo Nordisk UK Research Foundation;
                Award ID: NNF15OC0017622
                Award Recipient :
                Funded by: Psoriasisforeningen
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100008209, Robert Wehnerts og Kirsten Wehnerts Fond;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100008368, Gigtforeningen;
                Award ID: A2037
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100008368, Gigtforeningen;
                Award ID: A3570
                Award Recipient :
                Funded by: DERMBIO
                The work was funded by Psoriasisforeningen, Robert Wehnerts og Kirsten Wehnerts Fonden, Knud og Edith Eriksens Mindefond, Gigtforeningen (A2037, A3570), DERMBIO, and the Novo Nordisk Foundation (NNF15OC0017622). The Novo Nordisk Foundation provided support in form of a scholarship for author NDL, but did not have any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The rest of the Funders supported the study with funding for collection and analysis of biological material. MKA is employed by Zitelap Aps. Zitelap Aps provided support in the form of salary for author MKA and is responsible for management of the DERMBIO and DANBIO databases, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section.
                Categories
                Research Article
                Medicine and Health Sciences
                Rheumatology
                Arthritis
                Psoriatic Arthritis
                Medicine and Health Sciences
                Clinical Medicine
                Clinical Immunology
                Autoimmune Diseases
                Psoriasis
                Biology and Life Sciences
                Immunology
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                Autoimmune Diseases
                Psoriasis
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