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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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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-α (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 PCR-restriction 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.

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Acknowledgments

Zissis Mamuris and Angeliki Roussaki-Schulze contributed equally to this work.

We are very grateful to all participants in the study. The postgraduate programs ‘Biotechnology-Quality Assessment in Nutrition and the Environment’ and ‘Molecular Biology and Genetics Applications - Diagnostic Markers’ of the Department of Biochemistry and Biotechnology at the University of Thessaly, Greece, supported this work.

The authors have no conflicts of interest directly related to the content of this study.

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Authors and Affiliations

  1. Department of Biochemistry and Biotechnology, University of Thessaly, Ploutonos 26 and Aiolou Street, 41221, Larissa, Greece

    Yiannis Vasilopoulos, Marilena Manolika, Theologia Sarafidou, Vasilis Bagiatis & Zissis Mamuris

  2. Department of Dermatology, General University Hospital of Larissa, University of Thessaly, Larissa, Greece

    Efterpi Zafiriou & Angeliki Roussaki-Schulze

  3. Department of Dermatology, University Hospital of Heraklion, Heraklion, Crete, Greece

    Sabine Krüger-Krasagaki & Androniki Tosca

  4. 2nd Dermatology Department, Medical School, Aristotle University of Thessaloníki, Papageorgiou Hospital, Thessaloníki, Greece

    Aikaterini Patsatsi & Dimitris Sotiriadis

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  1. Yiannis Vasilopoulos
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  2. Marilena Manolika
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  3. Efterpi Zafiriou
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  5. Vasilis Bagiatis
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  6. Sabine Krüger-Krasagaki
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  7. Androniki Tosca
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  8. Aikaterini Patsatsi
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  9. Dimitris Sotiriadis
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  10. Zissis Mamuris
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  11. Angeliki Roussaki-Schulze
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Correspondence to Yiannis Vasilopoulos.

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Vasilopoulos, Y., Manolika, M., Zafiriou, E. et al. Pharmacogenetic Analysis of TNF, TNFRSF1A, and TNFRSF1B Gene Polymorphisms and Prediction of Response to Anti-TNF Therapy in Psoriasis Patients in the Greek Population. Mol Diagn Ther 16, 29–34 (2012). https://doi.org/10.1007/BF03256427

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