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

IF 2.9 3区医学 Q2 GENETICS & HEREDITY

Pharmacogenomics Journal Pub Date : 2022-10-13 DOI:10.1038/s41397-022-00291-7

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

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引用次数: 3

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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希腊银屑病患者环孢素治疗反应药物遗传学研究中的蛋白质网络和通路分析

尽管环孢素是治疗银屑病的一种行之有效的系统疗法，但患者的治疗反应却存在很大的异质性。我们的研究目的是根据 PICKLE 元数据库重建的环孢素通路相关蛋白-蛋白相互作用（PPI）网络，对 200 名希腊银屑病患者进行药物遗传学分析。通过使用 MassARRAY® 系统的 iPLEX®GOLD 面板，我们对映射到环孢素通路 22 个关键蛋白节点的 27 个单核苷酸多态性进行了基因分型。单SNP分析表明，经多重比较校正后，CALM1 rs12885713（P = 0.0108）和MALT1 rs2874116（P = 0.0006）多态性与环孢素治疗的阳性反应有统计学意义，而单倍型分析进一步提高了rs12885713作为环孢素治疗药物基因生物标记物的预测价值（P = 0.0173）。我们的研究结果有望改善我们对银屑病患者使用环孢素疗效和安全性的预测，并为复杂疾病的生物疗法药物遗传学提供框架。

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来源期刊

Pharmacogenomics Journal 医学-药学

CiteScore

7.20

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The Pharmacogenomics Journal is a print and electronic journal, which is dedicated to the rapid publication of original research on pharmacogenomics and its clinical applications. Key areas of coverage include: Personalized medicine Effects of genetic variability on drug toxicity and efficacy Identification and functional characterization of polymorphisms relevant to drug action Pharmacodynamic and pharmacokinetic variations and drug efficacy Integration of new developments in the genome project and proteomics into clinical medicine, pharmacology, and therapeutics Clinical applications of genomic science Identification of novel genomic targets for drug development Potential benefits of pharmacogenomics.