μ阿片受体A118G基因多态性预测盐酸羟考酮的镇痛效果

Association of Analgesic Effects of Oxycodone Hydrochloride with the A118G of OPRM1 Genes in Patients with Cancer Pain

目的探讨μ阿片受体(OPRMl)A118G基因多态性与盐酸羟考酮治疗癌痛效果的关系。方法重度癌痛患者59例,根据基因型的不同分为野生型纯合子(AA)组23例,突变型杂合子(AG)组28例,突变型纯合子(GG)组8例,分别口服盐酸羟考酮缓释片,比较治疗用量,记录相关的不良反应(包括恶心呕吐、眩晕、便秘等)。结果变异的等位基因频率(118G)为37.3%,AA组、AG组、GG组盐酸羟考酮缓释片使用量分别为(27.0±14.3),(36.4±22.5),(55.0±35.1)mg,差异有统计学意义(P=0.01)。不良反应中,恶心呕吐发生率为28.8%,眩晕发生率为22.0%,便秘发生率为52.5%,3组差异无统计学意义(P>0.05)。结论受阿片受体基因多态性的影响,盐酸羟考酮治疗癌痛疗效存在个体差异,G等位基因变异(AG或GG基因型)比AA基因型的患者需要更大剂量盐酸羟考酮镇痛,但其不良反应与基因多态性无关。

Objective To examine the relationship between the A118G polymorphism of mu-opioid receptor（OPRM1） gene and analgesic effects of oxycodone hydrochloride in patients with severe cancer pain. Methods Fifty-nine patients with severe cancer-induced pain were divided into 3 groups by genotype（AA group,AG group and GG group,23,28,8 patients, respectively）. They were orally treated with oxycodone hydrochloride sustained-release tablets,and the treatment dosage and adverse reactions（including nausea,vomiting,dizziness,constipation,etc.）were compared between groups. Results The variation of allele frequencies（118G）was 37.3%.The dosage of oxycodone hydrochloride sustained-release tablets used in AA, AG and GG groups was（27.0±14.3）,（36.4±22.5）and（55.0±35.1）mg,respectively,and the differences were statistically significant between groups（ P = 0. 01）. On the part of adverse reactions,the incidence of nausea and vomiting,dizziness, constipation was 28.8%,22.0%,and 52.5%,in AA,AG and GG groups,respectively,and there was no significant difference between groups（P〉0.05）. Conclusion The analgesic effect of oxycodone hydrochloride is affected by opioid receptor gene polymorphism.Patients with G allelic variation（AG or GG genotype）require larger doses of oxycodone hydrochloride than those with AA genotype.However,adverse reactions are not associated with polymorphism.