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

Antonatos, Charalabos; Patsatsi, Aikaterini; Zafiriou, Efterpi; Stavrou, Eleana F.; Liaropoulos, Andreas; Kyriakoy, Aikaterini; Evangelou, Evangelos; Digka, Danai; Roussaki-Schulze, Angeliki; Sotiriadis, D.; Georgiou, Sophia; Grafanaki, Katerina; Moschonas, Nicholas Κ.; Vasilopoulos, Yiannis

doi:10.1038/s41397-022-00291-7

Cited by 4 publications

(5 citation statements)

References 26 publications

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“…Additionally, Antonatos et al genotyped 27 SNPs mapped to 22 key protein nodes of the cyclosporine pathway in 200 Greek patients. Single-SNP analyses showed statistically significant associations between the rs12885713-T allele of CALM1 ( p = 0.0108) and the rs2874116-G allele of MALT1 ( p = 0.0006) genes with a positive response to cyclosporine after correction for multiple comparisons [ 58 ].…”

Section: Therapeutic Optionsmentioning

confidence: 99%

Genetic Influence on Treatment Response in Psoriasis: New Insights into Personalized Medicine

Berna-Rico,

Perez-Bootello,

Abbad-Jaime de Aragon

et al. 2023

IJMS

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Psoriasis is a chronic inflammatory disease with an established genetic background. The HLA-Cw*06 allele and different polymorphisms in genes involved in inflammatory responses and keratinocyte proliferation have been associated with the development of the disease. Despite the effectiveness and safety of psoriasis treatment, a significant percentage of patients still do not achieve adequate disease control. Pharmacogenetic and pharmacogenomic studies on how genetic variations affect drug efficacy and toxicity could provide important clues in this respect. This comprehensive review assessed the available evidence for the role that those different genetic variations may play in the response to psoriasis treatment. One hundred fourteen articles were included in this qualitative synthesis. VDR gene polymorphisms may influence the response to topical vitamin D analogs and phototherapy. Variations affecting the ABC transporter seem to play a role in methotrexate and cyclosporine outcomes. Several single-nucleotide polymorphisms affecting different genes are involved with anti-TNF-α response modulation (TNF-α, TNFRSF1A, TNFRSF1B, TNFAIP3, FCGR2A, FCGR3A, IL-17F, IL-17R, and IL-23R, among others) with conflicting results. HLA-Cw*06 has been the most extensively studied allele, although it has only been robustly related to the response to ustekinumab. However, further research is needed to firmly establish the usefulness of these genetic biomarkers in clinical practice.

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Section: Therapeutic Optionsmentioning

confidence: 99%

Genetic Influence on Treatment Response in Psoriasis: New Insights into Personalized Medicine

Berna-Rico,

Perez-Bootello,

Abbad-Jaime de Aragon

et al. 2023

IJMS

View full text Add to dashboard Cite

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“…Calmodulin (CALM1) is known as a calcium-dependent protein and is related to cell proliferation and epidermal hyperplasia in psoriasis [ 48 ]. In 200 Greek patients, the allele T of CALM1 rs12885713 displayed a significantly better response to cyclosporin (PASI75 at 3 months, p = 0.011) [ 49 ].…”

Section: Treatmentmentioning

confidence: 99%

“…MALT1 encodes MALT1 paracaspase, a potent activator of the transcription factors NF-κB and AP-1, and hence has a role in psoriasis [ 50 ]. MALT1 rs287411 allele G was associated with the effective response compared to allele A (PASI75 at 3 months, p < 0.001) [ 49 ].…”

Section: Treatmentmentioning

confidence: 99%

Pharmacogenomics on the Treatment Response in Patients with Psoriasis: An Updated Review

Wang

Chen

et al. 2023

IJMS

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The efficacy and the safety of psoriasis medications have been proved in trials, but unideal responses and side effects are noted in clinical practice. Genetic predisposition is known to contribute to the pathogenesis of psoriasis. Hence, pharmacogenomics gives the hint of predictive treatment response individually. This review highlights the current pharmacogenetic and pharmacogenomic studies of medical therapy in psoriasis. HLA-Cw*06 status remains the most promising predictive treatment response in certain drugs. Numerous genetic variants (such as ABC transporter, DNMT3b, MTHFR, ANKLE1, IL-12B, IL-23R, MALT1, CDKAL1, IL17RA, IL1B, LY96, TLR2, etc.) are also found to be associated with treatment response for methotrexate, cyclosporin, acitretin, anti-TNF, anti-IL-12/23, anti-IL-17, anti-PDE4 agents, and topical therapy. Due to the high throughput sequencing technologies and the dramatic increase in sequencing cost, pharmacogenomic tests prior to treatment by whole exome sequencing or whole genome sequencing may be applied in clinical in the future. Further investigations are necessary to manifest potential genetic markers for psoriasis treatments.

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“…Cyclosporine A (CsA) serves as an ideal therapeutic approach in the T cell-mediated pathogenesis of psoriasis, inhibiting the activation of the Nuclear Factor of Activated T cells and downstream IL-2 secretion ( Figure 1 ) [ 54 ]. Nevertheless, long-term administration of CsA is usually limited by ADRs, such as nephrotoxicity and hypertension [ 55 ].…”

Section: Traditional Therapiesmentioning

confidence: 99%

“…Novel approaches have also been conducted in the pharmacogenetics of CsA. Specifically, Antonatos and colleagues attempted to unravel the genetic predisposition of CsA response via reconstruction of the protein interactions during the drug’s mechanism of action and targeted genotyping, showing the association of two genetic variants ( CALM1 rs12885713, MALT1 rs2874116) with response to CsA treatment in 176 Greek psoriasis patients [ 54 ].…”

Section: Traditional Therapiesmentioning

confidence: 99%

Pharmaco-Omics in Psoriasis: Paving the Way towards Personalized Medicine

Antonatos

Asmenoudi

Panoutsopoulou

et al. 2023

IJMS

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The emergence of high-throughput approaches has had a profound impact on personalized medicine, evolving the identification of inheritable variation to trajectory analyses of transient states and paving the way for the unveiling of response biomarkers. The utilization of the multi-layered pharmaco-omics data, including genomics, transcriptomics, proteomics, and relevant biological information, has facilitated the identification of key molecular biomarkers that can predict the response to therapy, thereby optimizing treatment regiments and providing the framework for a tailored treatment plan. Despite the availability of multiple therapeutic options for chronic diseases, the highly heterogeneous clinical response hinders the alleviation of disease signals and exacerbates the annual burden and cost of hospitalization and drug regimens. This review aimed to examine the current state of the pharmaco-omic approaches performed in psoriasis, a common inflammatory disease of the skin. We sought to identify central studies that investigate the inter-individual variability and explore the underlying molecular mechanisms of drug response progression via biological profiling in psoriatic patients administered with the extended therapeutic armamentarium of psoriasis, incorporating conventional therapies, small molecules, as well as biological drugs that inhibit central pathogenic cytokines involved in the disease pathogenesis.

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

Cited by 4 publications

References 26 publications

Genetic Influence on Treatment Response in Psoriasis: New Insights into Personalized Medicine

Genetic Influence on Treatment Response in Psoriasis: New Insights into Personalized Medicine

Pharmacogenomics on the Treatment Response in Patients with Psoriasis: An Updated Review

Pharmaco-Omics in Psoriasis: Paving the Way towards Personalized Medicine

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