Baber M, Chaudhry S, Kelly L, Ross C, Carleton B, Berger H, Koren G
The Motherisk Program, Division of Clinical Pharmacology and Toxicology, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
Pharmacogenomics J. 2015 Oct;15(5):430-5. doi: 10.1038/tpj.2015.3. Epub 2015 Mar 10.
The objective of this study was to examine interindividual variability in codeine requirements and pain management by examining select genetic polymorphisms in the codeine pharmacological pathway. The study included a nested cohort of 98 women who were prescribed codeine following cesarean section. Participants were genotyped for select polymorphisms of the COMT, ABCB1, CYP2D6, UGT2B7 and OPRM1 genes and instructed to describe their level of pain using the visual analog scale (mm) 1 h following each dose of codeine. Analysis revealed that reported pain increases with maternal age (P=0.041). Asians required more codeine than Caucasians (P=0.048). Significant differences in mean dose consumption were seen among the genotypic groups of the OPRM1 A118G (P=0.001) and UGT2B7 C802T (P=0.015) variants. These variants were found to predict codeine consumption in the cohort overall (P=0.000) and among Caucasians (P=0.001). These findings will assist in customizing therapy to effectively manage postpartum pain.
本研究的目的是通过检测可待因药理途径中的特定基因多态性，来研究可待因需求量和疼痛管理的个体间差异。该研究纳入了一个嵌套队列，其中98名女性在剖宫产术后被开具了可待因处方。对参与者的儿茶酚-O-甲基转移酶（COMT）、ATP结合盒转运蛋白B1（ABCB1）、细胞色素P450 2D6（CYP2D6）、尿苷二磷酸葡萄糖醛酸基转移酶2B7（UGT2B7）和μ-阿片受体（OPRM1）基因的特定多态性进行基因分型，并指导她们在每次服用可待因后1小时使用视觉模拟量表（mm）描述自己的疼痛程度。分析显示，报告的疼痛程度随产妇年龄增加而升高（P = 0.041）。亚洲人比高加索人需要更多的可待因（P = 0.048）。在OPRM1 A118G（P = 0.001）和UGT2B7 C802T（P = 0.015）变体的基因型组之间，平均剂量消耗量存在显著差异。这些变体被发现可预测整个队列（P = 0.000）以及高加索人群（P = 0.001）中的可待因消耗量。这些发现将有助于定制治疗方案，以有效管理产后疼痛。
