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dc.creatorVasilopoulos, Y.en
dc.creatorManolika, M.en
dc.creatorZafiriou, E.en
dc.creatorSarafidou, T.en
dc.creatorBagiatis, V.en
dc.creatorKrüger-Krasagaki, S.en
dc.creatorTosca, A.en
dc.creatorPatsatsi, A.en
dc.creatorSotiriadis, D.en
dc.creatorMamuris, Z.en
dc.creatorRoussaki-Schulze, A.en
dc.description.abstractBackground: Although biologic therapies have revolutionized the treatment of psoriasis, patients exhibit a substantial heterogeneous response that could be due to complex genetic heterogeneity. Objective: The aim of this study was to investigate the possible influence of tumor necrosis factor-a (TNF), TNF receptor I (TNFRSF1A), and TNF receptor II (TNFRSF1B) gene polymorphisms on anti-TNF treatment responsiveness in psoriasis patients. Methods: A Greek multicenter collaboration was established to recruit a cohort of patients (n = 80) with psoriasis treated with anti-TNF drugs. Single nucleotide polymorphisms (SNPs) in TNF (-238G>A, -308G>A, -857C>T), TNFRSF1A (36A>G), and TNFRSF1B (676T>G) were genotyped by PCRrestriction fragment length polymorphism assays. SNPs and haplotypes, including stratification by comorbidity status, were analyzed for association with treatment response after 6 months of therapy, defined as a reduction in the Psoriasis Area and Severity Index (PASI) score by >75% (responders) or ≤50% (nonresponders). Results: Sixty-three patients (78.8%) were defined as responders (PASI score reduction >75%) and 17 patients (21.2%) were defined as nonresponders (PASI score reduction ≤50%). Carriage of TNF -857C or TNFRSF1B 676T alleles was associated with positive response to drug treatment in patients treated with etanercept (p = 0.002 and p = 0.001, respectively). None of the genotyped SNPs were associated with responsiveness to treatment with infliximab or adalimumab. Additionally, when patients were stratified by comorbidity status, none of the genotyped SNPs were alone associated with responsiveness to drug treatment. Conclusion: This study is the first in the field of psoriasis demonstrating a strong association between genetic markers and positive response to drug treatment. Validation of this result in larger studies, as well as analysis of other drug treatments, could provide the basis for individually tailored treatment, along with increased cost effectiveness and reduced unnecessary exposure to toxicity. ©2012 Adis Data Information BV. All rights reserved.en
dc.subjectgenomic DNAen
dc.subjecttumor necrosis factoren
dc.subjecttumor necrosis factor receptor 1en
dc.subjecttumor necrosis factor receptor 2en
dc.subjectcohort analysisen
dc.subjectdisease durationen
dc.subjectdisease severityen
dc.subjectgenetic polymorphismen
dc.subjectmajor clinical studyen
dc.subjectpolymerase chain reactionen
dc.subjectpopulation geneticsen
dc.subjectpriority journalen
dc.subjectPsoriasis Area and Severity Indexen
dc.subjectPsoriasis Severity Indexen
dc.subjectrestriction fragment length polymorphismen
dc.subjectscoring systemen
dc.subjectsingle nucleotide polymorphismen
dc.subjecttreatment responseen
dc.subjectAnti-Inflammatory Agentsen
dc.subjectAntibodies, Monoclonalen
dc.subjectCohort Studiesen
dc.subjectGenetic Predisposition to Diseaseen
dc.subjectMiddle Ageden
dc.subjectPolymorphism, Single Nucleotideen
dc.subjectReceptors, Tumor Necrosis Factor, Type Ien
dc.subjectReceptors, Tumor Necrosis Factor, Type IIen
dc.subjectRetrospective Studiesen
dc.subjectTumor Necrosis Factorsen
dc.titlePharmacogenetic analysis of TNF, TNFRSF1A, and TNFRSF1B gene polymorphisms and prediction of response to anti-TNF therapy in psoriasis patients in the greek populationen

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