Anesthesia and Intensive Care Unit, Azienda Ospedaliero Universitaria delle Marche, via Conca 71, Torrette di Ancona, 60126, Italy.
Department of Biomedical Sciences and Public Health, Università Politecnica Delle Marche, via Tronto 10/a, Torrette di Ancona, 60020, Italy.
BMC Anesthesiol. 2023 Feb 16;23(1):55. doi: 10.1186/s12871-023-02018-y.
Pharmacogenetics could represent a further resource to understand the interindividual heterogeneity of response of the host to sepsis and to provide a personalized approach to the critical care patient.
Secondary analysis of data from the prospective observational study NCT02750163, in 50 adult septic and septic shock patients treated with Acetaminophen (ACT) for pyrexia. We investigated the presence of two polymorphisms, located respectively in the genes UGT1A1 and CYP3A5, that encode for proteins related to the hepatic metabolism of ACT. The main dependent variables explored were plasmatic concentration of ACT, body temperature and hepatic parameters.
8% of the patients carried CYP3A5 rs776746 A/G genotypes and showed significantly higher plasma levels of ACT than GG wild type patients, and than patients with UGT1A1 rs8330 C/G genotypes.
Identifying specific genotypes of response to ACT may be helpful to guide a more personalized titration of therapy in sepsis and septic shock. CYP3A5 might be a good biomarker for ACT metabolism; however further studies are needed to confirm this result.
NCT02750163.
药物遗传学可能是进一步了解宿主对脓毒症反应个体差异的资源，并为重症患者提供个性化治疗方法。
对前瞻性观察研究 NCT02750163 的数据进行二次分析，该研究纳入了 50 例接受醋氨酚（ACT）退热治疗的成年脓毒症和脓毒性休克患者。我们研究了两个分别位于 UGT1A1 和 CYP3A5 基因中的多态性，这些基因编码与 ACT 肝代谢相关的蛋白。主要探索的因变量是 ACT 的血浆浓度、体温和肝参数。
8%的患者携带 CYP3A5 rs776746 A/G 基因型，其 ACT 血浆水平明显高于 GG 野生型患者，也高于 UGT1A1 rs8330 C/G 基因型患者。
确定对 ACT 的特定反应基因型可能有助于指导脓毒症和脓毒性休克的个体化治疗滴定。CYP3A5 可能是 ACT 代谢的良好生物标志物；然而，需要进一步的研究来证实这一结果。
NCT02750163。
