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Protein network and pathway analysis in a pharmacogenetic study of cyclosporine treatment response in Greek patients with psoriasis

The Pharmacogenomics Journal volume 23, pages 8–13 (2023)Cite this article

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Abstract

Although cyclosporine comprises a well-established systemic therapy for psoriasis, patients show important heterogeneity in their treatment response. The aim of our study was the pharmacogenetic analysis of 200 Greek patients with psoriasis based on the cyclosporine pathway related protein-protein interaction (PPI) network, reconstructed through the PICKLE meta-database. We genotyped 27 single nucleotide polymorphisms, mapped to 22 key protein nodes of the cyclosporine pathway, via the utilization of the iPLEX®GOLD panel of the MassARRAY® System. Single-SNP analyses showed statistically significant associations between CALM1 rs12885713 (P = 0.0108) and MALT1 rs2874116 (P = 0.0006) polymorphisms with positive response to cyclosporine therapy after correction for multiple comparisons, with the haplotype analyses further enhancing the predictive value of rs12885713 as a pharmacogenetic biomarker for cyclosporine therapy (P = 0.0173). Our findings have the potential to improve our prediction of cyclosporine efficacy and safety in psoriasis patients, as well as provide the framework for the pharmacogenetics of biological therapies in complex diseases.

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Fig. 1: The protein-protein interaction network of the core proteins participating in the CsA mechanism of action.

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Data availability

Data are available upon request from the corresponding author.

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Acknowledgements

This work was partially funded by the MSc “Toxicology” program, University of Thessaly. This work was also supported by the project “Infrastructure for preclinical and early-phase clinical development of drugs, therapeutics and biomedical devices (EATRIS-GR)” (MIS 5028091: EATRIS-GR-UPatras, co-PI: NKM) which is implemented under the Action “Reinforcement of the Research and Innovation Infrastructure”, funded by the Operational Programme “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014-2020) and cofinanced by Greece and the European Union (European Regional Development Fund).

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Authors and Affiliations

  1. Laboratory of Genetics, Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, Patras, Greece

    Charalabos Antonatos, Eleana F. Stavrou, Andreas Liaropoulos, Danai Digka & Yiannis Vasilopoulos

  2. 2nd Dermatology Department, Medical School, Papageorgiou Hospital, Aristotle University, Thessaloniki, Greece

    Aikaterini Patsatsi, Aikaterini Kyriakoy & Dimitris Sotiriadis

  3. Department of Dermatology, University General Hospital Larissa, University of Thessaly, Volos, Greece

    Efterpi Zafiriou & Angeliki Roussaki-Schulze

  4. Lab. of General Biology, Medical School, University of Patras, Patras, Greece

    Eleana F. Stavrou & Nicholas Κ. Moschonas

  5. Department of Hygiene and Epidemiology, Medical School, University of Ioannina, Ioannina, Greece

    Evangelos Evangelou

  6. Department of Epidemiology & Biostatistics, MRC Centre for Environment and Health, Imperial College London, London, UK

    Evangelos Evangelou

  7. Department of Biomedical Research, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Ioannina, Greece

    Evangelos Evangelou

  8. Dermatology Department, Medical School, University of Patras, Patras, Greece

    Sophia Georgiou & Katerina Grafanaki

  9. Foundation of Research & Technology, Institute of Chemical Engineering Science (ICE-HT), Patras, Greece

    Nicholas Κ. Moschonas

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  1. Charalabos Antonatos
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Contributions

Participated in research design: YV and NKM; Sample isolation: AK, EZ, AK, AR-S, DS, SG, KG; Conducted experiments: CA, EFS, AL, DD; Performed data analysis: CA, EE; Write or contributed to the manuscript preparation: CA, AP, EZ, EFS, AL, AK, EE, DD, AR-S, DS, SG, KG, NKM, YV. All authors agree with the submission of this manuscript and agree to be accountable for all aspects of this study.

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Correspondence to Yiannis Vasilopoulos.

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Antonatos, C., Patsatsi, A., Zafiriou, E. et al. Protein network and pathway analysis in a pharmacogenetic study of cyclosporine treatment response in Greek patients with psoriasis. Pharmacogenomics J 23, 8–13 (2023). https://doi.org/10.1038/s41397-022-00291-7

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