CYP3A4*1G基因多态性对病人芬太尼镇痛效应的影响

目的 探讨CYP3A4*IG基因多态性对病人芬太尼镇痛效应的影响.方法 择期全麻下子宫肌瘤剔除术或子宫全切手术病人139例,河南籍,汉族,年龄20～50岁,ASA Ⅰ或Ⅱ级.采用聚合酶链反应-限制性片段长度多态性技术,进行CYP3A4*1G多态性位点的检测,根据基因型将病人分成野生型纯合子组、突变型杂合子组和突变型纯合子组.病人清醒后行视觉模拟评分(VAS),当VAS超过3分时,则间断静脉注射芬太尼20 μg,直至VAS≤3分时开始病人自控静脉镇痛,维持VAS不超过4分,记录病人自控静脉镇痛24 h内芬太尼的用量.结果 与突变型纯合子组比较,突变型杂合子组和野生型纯合子组病人自控静脉镇痛24 h内芬太尼用量增多(P<0.05),突变型杂合子组和野生型纯合子组该指标差异无统计学意义(P>0.05).结论 CYP3A4*1G基因多态性是引起芬太尼药效学个体差异的遗传因素之一.

Effects of CYP3A4* IG genetic polymorphism on analgesia with fentanyl

Objective To investigate the effects of CYP3A4* IG genetic polymorphism on analgesia with fentanyl. Methods One hundred and thirty-nine ASA Ⅰ or Ⅱ patients, aged 20-50 yr, Han nationality, Henan province, scheduled for elective myomectomy or abdominal total hysterectomy under general anesthesia, were enrolled in this study. The polymorphic sites of the CYP3A4* 1G allele were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The patients were assigned to one of 3 groups according to their genotypes: wild homozygote group (w/w), mutation heterozygote group (m/w) and mutation homozygote group (m/m). The patients' pain was assessed with visual analog scale (VAS) after consciousness was regained. If VAS score > 3, the patients were given fantanyl 20 μg every 5 min until VAS score ≤ 3, and PCIA with fentanyl was then started. The background infusion rate of fentanyl 1.0 mg and droperidol 5 mg in 100 ml normal saline was 0.5 ml/h. The PCIA pump was programmed to allow a 2 ml bolus of fentanyl solution with a 5 min lockout interval, 7 time successful delivery per hour and maximum dosage 145 μg per hour, and VAS score was maintained less than 4. The amount of fentanyl used within 24 h during PCIA was also recorded. Results One hundred and thirty-six patients completed the study. Their genotypes were w/w 73; in/w 54; m/m 9. The amount of fentanyl used within 24 h during PCIA was significantly larger in group m/w and w/w than in group m/m (P<0.05), but there was no significant difference in this index between group m/w and w/w (P > 0.05) .Conclusion CYP3A4* 1G genetic polymorphism is one of the factors contributing to the individual variation in patient's response to analgesia with fentanyl.