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

ABSTRACT: 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.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.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.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.

SUBMITTER: Loft ND

PROVIDER: S-EPMC5794107 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Loft Nikolai Dyrberg ND Skov Lone L Rasmussen Mads Kirchheiner MK Gniadecki Robert R Dam Tomas Norman TN Brandslund Ivan I Hoffmann Hans Jürgen HJ Andersen Malene Rohr MR Dessau Ram Benny RB Bergmann Ann Christina AC Andersen Niels Møller NM Abildtoft Mikkel Kramme MK Andersen Paal Skytt PS Hetland Merete Lund ML Glintborg Bente B Bank Steffen S Vogel Ulla U Andersen Vibeke V

PloS one 20180201 2

<h4>Background</h4>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.<h4>Methods</h4>Using a candidate gene approach, we studied 53 single nucleotide polymorphisms ...[more]

PMID: 29389950

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Project description:IntroductionPsoriatic arthritis (PsA) is a chronic, inflammatory arthritis that affects an estimated 30% of patients with psoriasis. PsA is underdiagnosed in primary care and dermatology clinics due to a variety of reasons, including failure of healthcare providers to ask about symptoms, overlap of symptoms and signs with other rheumatologic conditions, and lack of a specific diagnostic test. A delay in PsA diagnosis and treatment, even as short as 6 months, can lead to decreased quality of life, increased joint damage, and worse long-term physical function. In this study, we sought to identify the clinical and genetic factors that help discriminate patients with PsA from those with cutaneous psoriasis only.MethodsWe analyzed a cohort of 974 psoriasis patients at an academic medical center, of whom 175 had confirmed PsA, and performed univariate, multivariate, and predictive modeling to determine factors associated with PsA.ResultsThe univariate analysis revealed significant positive associations of PsA with age, nail involvement, scalp involvement, skin fold involvement, elbow/knee involvement, psoriasis severity, plaque subtype, erythrodermic subtype, hypertension, type 2 diabetes, and coronary artery disease, and a significant negative association of PsA with the human leukocyte antigen (HLA)-C*06:02 allele. In the multivariate analysis, nail involvement, type 2 diabetes, and pustular psoriasis remained significantly associated with PsA, while HLA-C*06:02 positivity remained protective. There was a trend towards an association of PsA with older age, younger age of psoriasis onset, and skin fold involvement, while there was protective trend for smoking. A predictive model including both clinical and genetic factors showed reasonable discriminative ability between psoriasis and PsA, with an area under the curve of 0.87 for a receiver operating characteristic curve.ConclusionThis study identified a number of clinical and genetic features that could help stratify patients who are at higher risk for having PsA and for whom rheumatology referral may be beneficial.

Project description:BACKGROUND:The early detection of psoriatic arthritis (PSA) poses a challenge to rheumatologists, even when their diagnosis is aided by sonography. In order to facilitate early detection of PSA among patients with psoriasis (PSO), we retrospectively analyzed of the relationships between serological markers and comorbidities in 629 psoriatic patients, 102 of which had PSA, while the other 527 had PSO. RESULTS:Serological markers were found not to be useful in distinguishing between PSA and PSO (p >?0.05 for all comparisons). The prevalence rate of PSA among PSO patients was around 19.4%. Two components of metabolic syndrome-hyperlipidemia (2.94%) and gout (4.9%)-were significantly more prevalent in PSA patients than in PSO patients (p <?0.05). The odds ratio for PSA is 15.94 in patients with hyperlipidemia with a 95% confidence interval (CI) of 1.64-154.80; meanwhile, the odds ratio for PSA is 3.83 in patients with gout with a 95% CI of 1.19-12.31. Allergic rhinitis (5.88%) was more prevalent in PSA patients than in PSO patients (p <?0.01). The odds ratio was 8.17 in patients with allergic rhinitis with a 95% CI of 2.26-29.50. Plasma hs-miR-210-3p distinguishes PSA from PSO, and its levels can also be distinguished from PSA after treated with anti-TNF? biologics agents (both p <?0.05). CONCLUSIONS:No clinical available serology markers, but hyperlipidemia, gout, axial spondylopathy (inflammatory back pain), or allergic rhinitis, could differentiate between psoriatic arthritis from psoriasis. Plasma hs-miR-210-3p and comorbidities may differentiate psoriatic arthritis from psoriasis. Key Points • Clinical manifestations and comorbidities are different between psoriatic arthritis and psoriasis only patients. • Traditional serology markers are similar between psoriatic arthritis and psoriasis-only patients. • Plasma hs-miR-210-3p distinguishes PSA from PSO, and its levels can also be distinguished from PSA after treated with anti-TNF? biologics agents in our study.

Project description:Psoriatic arthritis (PsA) is a chronic, systemic inflammatory disease. Up to 40 % of patients with psoriasis will go on to develop PsA, usually within 5-10 years of cutaneous disease onset. Both conditions share common pathogenic mechanisms involving genetic and environmental factors. Because psoriasis is typically present for years before PsA-related joint symptoms emerge, dermatologists are in a unique position to detect PsA earlier in the disease process through regular, routine screening of psoriasis patients. Distinguishing clinical features of PsA include co-occurrence of psoriatic skin lesions and nail dystrophy, as well as dactylitis and enthesitis. Patients with PsA are usually seronegative for rheumatoid factor, and radiographs may reveal unique features such as juxta-articular new bone formation and pencil-in-cup deformity. Early treatment of PsA with disease-modifying anti-rheumatic drugs has the potential to slow disease progression and maintain patient quality of life. Optimally, a single therapeutic agent will control both the skin and joint psoriatic symptoms. A number of traditional treatments used to manage psoriasis, such as methotrexate and cyclosporine, are also effective for PsA, but these agents are often inadequately effective, temporary in benefit and associated with significant safety concerns. Biologic anti-tumour necrosis factor agents, such as etanercept, infliximab and adalimumab, are effective for treating patients who have both psoriasis and PsA. However, a substantial number of patients may lose efficacy, have adverse effects or find intravenous or subcutaneous administration inconvenient. Emerging oral treatments, including phosphodiesterase 4 inhibitors, such as apremilast, and new biologics targeting interleukin-17, such as secukinumab, brodalumab and ixekizumab, have shown encouraging clinical results in the treatment of psoriasis and/or PsA. Active and regular collaboration of dermatologists with rheumatologists in managing patients who have psoriasis and PsA is likely to yield more optimal control of psoriatic dermal and joint symptoms, and improve long-term patient outcomes.

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

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

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