Laboratory of Genetics, Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, Patras, Greece.
2nd Dermatology Department, Medical School, Papageorgiou Hospital, Aristotle University, Thessaloniki, Greece.
Pharmacogenomics J. 2023 Jan;23(1):8-13. doi: 10.1038/s41397-022-00291-7. Epub 2022 Oct 13.
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.
尽管环孢素是一种成熟的治疗银屑病的系统疗法，但患者在治疗反应方面存在显著的异质性。我们的研究目的是对 200 名希腊银屑病患者进行基于环孢素通路相关蛋白-蛋白相互作用（PPI）网络的药物遗传学分析，该网络是通过 PICKLE 元数据库重建的。我们通过利用 MassARRAY®系统的 iPLEX®GOLD 面板，对 22 个关键蛋白节点映射的 27 个单核苷酸多态性进行了基因分型。单核苷酸多态性分析显示，CALM1 rs12885713（P = 0.0108）和 MALT1 rs2874116（P = 0.0006）多态性与环孢素治疗后的阳性反应之间存在统计学意义上的关联，经多重比较校正后，单体型分析进一步增强了 rs12885713 作为环孢素治疗药物遗传学生物标志物的预测价值（P = 0.0173）。我们的发现有可能改善我们对银屑病患者环孢素疗效和安全性的预测，并为复杂疾病的生物治疗药物遗传学提供框架。
