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.

尽管环孢菌素是一种行之有效的银屑病全身疗法，但患者在治疗反应中表现出重要的异质性。我们研究的目的是基于通过 PICKLE 元数据库重建的环孢菌素通路相关蛋白-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。我们通过利用 MassARRAY® 系统的 iPLEX®GOLD panel，对 27 个单核苷酸多态性进行了基因分型，映射到环孢菌素途径的 22 个关键蛋白质节点。单 SNP 分析显示CALM1 rs12885713 ( P  = 0.0108) 和MALT1 rs2874116 ( P = 0.0006) 校正多重比较后对环孢菌素治疗有阳性反应的多态性，单倍型分析进一步增强了 rs12885713 作为环孢菌素治疗的药物遗传学生物标志物的预测价值 ( P  = 0.0173)。我们的研究结果有可能改进我们对环孢菌素在银屑病患者中的疗效和安全性的预测，并为复杂疾病的生物疗法的药物遗传学提供框架。