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遗传变异对接受全身麻醉的约旦阿拉伯患者异丙酚剂量和反应的影响。

Effects of Genetic Variants on the Propofol Dose and Response among Jordanian Arabic Patients Undergoing General Anesthesia.

机构信息

Department of Anesthesia, the University of Jordan Hospital, Amman, Jordan.

Department of Biological Sciences, School of Science, The University of Jordan, Amman, Jordan.

出版信息

Curr Drug Metab. 2023;23(14):1156-1161. doi: 10.2174/1389200224666230130110350.

DOI:10.2174/1389200224666230130110350
PMID:36717987
Abstract

BACKGROUND

Propofol is the most commonly used general anesthetic drug in many countries, including Jordan. However, there is a wide variation in the propofols' dose and response among the patients. Genetic variation in the cytochrome (CYP) 2B6 gene affects propofol metabolism and might affect propofol dose and response.

AIMS

This study aimed to determine the influence of major genetic alleles of the CYP2B6 gene, CYP2B6*2A, *6A, *3, *4A, and *5A, on the required propofol dose and response among Jordanian Arabic patients attending The University of Jordan Hospital.

METHODS

A total of 155 patients were administrated propofol. The propofol response was evaluated by monitoring the time to reach the bispectral index of 60 (BIS60) for every patient. The CYP2B6 genetic variants were genotyped by polymerase chain reaction followed by restriction through specific enzymes for CYP2B6 variants.

RESULTS

It is found that patients with variant CYP2B6*2A and 4A alleles required significantly (P < 0.05) lower propofol doses, while patients with variant CYP2B66A, 3, and 5A alleles required higher propofol doses in comparison with patients carrying the wild CYP2B6 alleles. Patients with variant CYP2B62A and 3 alleles needed a significantly (P < 0.05) shorter while patients with variant CYP2B65A allele needed longer time of BIS than patients with wild CYP2B62A, *3, and *5A alleles.

CONCLUSION

It is concluded that CYP2B6 genetic variants affect propofol dose and can explain, at least partly, the inter-individual variation in the propofol response. Further clinical studies with a larger sample size are needed to confirm the findings of this study.

摘要

背景

丙泊酚是包括约旦在内的许多国家最常用的全身麻醉药物。然而,患者之间的丙泊酚剂量和反应存在很大差异。细胞色素(CYP)2B6 基因的遗传变异会影响丙泊酚的代谢,可能会影响丙泊酚的剂量和反应。

目的

本研究旨在确定 CYP2B6 基因的主要遗传等位基因 CYP2B6*2A、*6A、*3、4A 和5A 对约旦阿拉伯患者在约旦大学医院接受丙泊酚的剂量和反应的影响。

方法

共给 155 名患者使用丙泊酚。通过监测每位患者达到双谱指数 60(BIS60)的时间来评估丙泊酚的反应。通过聚合酶链反应(PCR)和特定酶对 CYP2B6 变体进行限制来对 CYP2B6 遗传变异进行基因分型。

结果

研究发现,携带变异 CYP2B62A 和4A 等位基因的患者需要的丙泊酚剂量显著(P < 0.05)降低,而携带 CYP2B66A、3 和5A 等位基因的患者需要的丙泊酚剂量则高于携带野生 CYP2B6 等位基因的患者。携带变异 CYP2B62A 和3 等位基因的患者需要的 BIS 时间显著(P < 0.05)缩短,而携带变异 CYP2B65A 等位基因的患者需要的 BIS 时间则长于携带野生 CYP2B6*2A、3 和5A 等位基因的患者。

结论

CYP2B6 遗传变异影响丙泊酚剂量,至少可以部分解释丙泊酚反应的个体差异。需要进行更大样本量的进一步临床研究来证实本研究的结果。

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