多巴胺受体D2基因多态性对汉族患者疼痛敏感度及术后阿片药物镇痛剂量的影响

Effects of DRD2 polymorphisms on pain sensitivity and postoperative opioids dose in Chinese Han population postoperative pain patients

摘要:

【摘要】 目的 探讨多巴胺受体D2基因（DRD2）多态性（rs6276、rs4274224）、疼痛敏感度及术后阿片药物用量的关系。方法 择期行上腹部手术的汉族患者133例，利用便携式压力测试仪，测定患者的试验性疼痛压力痛阈（PPT）和耐痛阈（PTO），抽取外周静脉血，采用聚合酶链反应-限制性片段长度多态性技术（PCR-RFLP）对DRD2基因多态性位点（rs6276、rs4274224）进行检测。记录患者术后6、12、24、48 h的疼痛视觉模拟评分（VAS）并统计48 h内镇痛不全比例。结果 133例患者中，DRD2（rs6276、rs4274224）等位基因发生频率均符合Hardy-Weinberg平衡，rs6276的基因型患者分布频率分别为A/A（24.1％）、A/G（50.4％）、G/G（25.6％），rs4274224的基因型患者分布频率分别为A/A（20.3％）、A/G（53.4％）、G/G（26.3.0％）。rs6276各组基因型患者PPT比较及PTO比较，A/A基因型患者PPT及PTO值均显著高于其他基因型患者，差异有统计学意义（P＜0. 05）。术后VAS评分显示rs6276基因型A/A的患者在术后6h、12h、24h、48h VAS评分均显著低于其他基因型患者（P＜0. 05）。不同基因型阿片用量及镇痛不全比例比较，A/G、G/G基因型患者舒阿片用量及镇痛不全比例低均高于A/A基因型，差异均有统计学意义（P＜0. 05）。rs4274224的三种基因型与PPT、PTO和阿片镇痛用量比较，差异均无统计学意义。结论 DRD2 rs6276基因多态性与汉族疼痛敏感性相关，可能影响患者术后阿片镇痛剂量，而DRD2 rs4274224可能与汉族疼痛敏感性及术后阿片镇痛剂量无关。

Abstract:

Abstract：Objective To investigate the association between DRD2 polymorphisms, pain sensitivity and postoperative opioids dose in Chinese Han population postoperative pain patients. Methods 133 Chinese Han population patients scheduled to undergo upper abdominal surgery were enrolled. Pressure pain threshold (PPT) and pain tolerance domain (PTO) of patients were detected by stress stimulation. The venous blood of patients was collected and DRD2 gene polymorphism (rs6276、rs4274224) was detected by polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP). The visual analogue scale (VAS) scores were recorded in 6 h, 12 h, 24 h and 48 h after surgery. The rate of incomplete analgesia patients was also recorded in all groups. Results The genetic polymorphisms of DRD2 (rs6276、rs4274224) were consistent with Hardy-Weinberg equilibrium in 133 patients. The distribution frequencies of rs6276 genotype were A/A (24.1％), A/G (50.4％) and G/G (25.6％) while the distribution frequencies of rs4274224 were A/A (20.3％), A/G (53.4％) and G/G (26.3％). As for rs6276 polymorphism, the A/A genotype patients had higher PPT and PTO, comparing with individuals with genotypes coding for A/G and A/A (P<0.05). The VAS scores of A/A genotype patients were significant lower than other genotypes in each group (P<0.05). Patients with different genotype were different in the dosage of opioids and the rate of inadequate analgesia, A/G and G/G patients were higher than A/A patients in the dosage of opioids and rate of inadequate analgesia (P<0.05). There was no association between DRD2 rs4274224 genetic polymorphism, PPT, PTO and opioids dose. Conclusion DRD2 rs6276 gene polymorphism is associated with pain sensitivity, which could influence the analgesic dosage of opioids after surgery. The DRD2 rs4274224 gene polymorphism may be not associated with PPT, PTO and opioids dose.