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  •   University of Thessaly Institutional Repository
  • Επιστημονικές Δημοσιεύσεις Μελών ΠΘ (ΕΔΠΘ)
  • Δημοσιεύσεις σε περιοδικά, συνέδρια, κεφάλαια βιβλίων κλπ.
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  •   University of Thessaly Institutional Repository
  • Επιστημονικές Δημοσιεύσεις Μελών ΠΘ (ΕΔΠΘ)
  • Δημοσιεύσεις σε περιοδικά, συνέδρια, κεφάλαια βιβλίων κλπ.
  • View Item
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Pharmacogenetic analysis of TNF, TNFRSF1A, and TNFRSF1B gene polymorphisms and prediction of response to anti-TNF therapy in psoriasis patients in the greek population

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Author
Vasilopoulos, Y.; Manolika, M.; Zafiriou, E.; Sarafidou, T.; Bagiatis, V.; Krüger-Krasagaki, S.; Tosca, A.; Patsatsi, A.; Sotiriadis, D.; Mamuris, Z.; Roussaki-Schulze, A.
Date
2012
DOI
10.2165/11594660
Keyword
adalimumab
etanercept
genomic DNA
infliximab
tumor necrosis factor
tumor necrosis factor receptor 1
tumor necrosis factor receptor 2
adult
article
cohort analysis
disease duration
disease severity
female
genetic polymorphism
Greece
haplotype
human
major clinical study
male
pharmacogenetics
polymerase chain reaction
population genetics
priority journal
psoriasis
Psoriasis Area and Severity Index
Psoriasis Severity Index
restriction fragment length polymorphism
scoring system
single nucleotide polymorphism
treatment response
Anti-Inflammatory Agents
Antibodies, Monoclonal
Cohort Studies
Genetic Predisposition to Disease
Genotype
Humans
Middle Aged
Polymorphism, Single Nucleotide
Receptors, Tumor Necrosis Factor, Type I
Receptors, Tumor Necrosis Factor, Type II
Retrospective Studies
Tumor Necrosis Factors
Metadata display
Abstract
Background: 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.
URI
http://hdl.handle.net/11615/34382
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  • Δημοσιεύσεις σε περιοδικά, συνέδρια, κεφάλαια βιβλίων κλπ. [19705]

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