De Pieri Marco, Ferrari Marco, Marino Franca, Traber Rafael, Bolla Emilio, Cosentino Marco
Center for Research in Medical Pharmacology, University of Insubria, Varese, Italy.
PhD Program in Clinical and Experimental Medicine and Medical Humanities, University of Insubria, Varese, Italy.
Front Pharmacol. 2023 May 9;14:1182393. doi: 10.3389/fphar.2023.1182393. eCollection 2023.
Cariprazine (CAR) is an antipsychotic drug for the treatment of schizophrenia (SCZ) and bipolar disorder (BD), and it acts as a partial agonist on the dopamine receptors (DR), D2, and D3. Although many single nucleotide polymorphisms (SNPs) in genes coding for these receptors are known to influence response to antipsychotics, to date, no study on CAR pharmacogenetics exists. In this pilot study, we investigated the relationship between SNPs in DRD2 (rs1800497 and rs6277) and DRD3 (rs6280), and response to CAR treatment, evaluated by the psychometric Brief Psychiatric Rating Scale (BPRS), in a cohort of Caucasian patients. We found a significant association between DRD2 rs1800497 and rs6277 and response to CAR treatment. When genotypes were combined into an arbitrary score, the receiver operating characteristic curve analysis showed that using a cut-off value of -2.5 the response to CAR treatment could be predicted with a positive likelihood ratio of 8.0. Our study report, for the first time, a correlation between SNPs in DRD2 and response to CAR treatment. After confirmation in a larger cohort of patients, our results could open the way for the identification of new tools for the provision of response to CAR treatment.
卡立普嗪（CAR）是一种用于治疗精神分裂症（SCZ）和双相情感障碍（BD）的抗精神病药物，它是多巴胺受体（DR）D2和D3的部分激动剂。虽然已知编码这些受体的基因中有许多单核苷酸多态性（SNP）会影响对抗精神病药物的反应，但迄今为止，尚无关于卡立普嗪药物遗传学的研究。在这项初步研究中，我们调查了白种人患者队列中DRD2（rs1800497和rs6277）和DRD3（rs6280）中的SNP与通过心理测量简明精神病评定量表（BPRS）评估的卡立普嗪治疗反应之间的关系。我们发现DRD2 rs1800497和rs6277与卡立普嗪治疗反应之间存在显著关联。当将基因型合并为一个任意分数时，受试者工作特征曲线分析表明，使用-2.5的临界值可以预测卡立普嗪治疗反应，阳性似然比为8.0。我们的研究首次报告了DRD2中的SNP与卡立普嗪治疗反应之间的相关性。在更大的患者队列中得到证实后，我们的结果可能为识别预测卡立普嗪治疗反应的新工具开辟道路。
