CYP3A4*1G、OPRM1 A118G基因多态性与腹腔镜结肠肿瘤根治术患者围术期芬太尼用量和VAS评分的关系分析

Analysis on relationships between CYP3A4*1G and OPRM1 A118G gene polymorphisms with perioperative fentanyl dosage and VAS score in patients with laparoscopic colon tumor radical operation

目的在接受腹腔镜结肠肿瘤根治术患者中,探讨CYP3A4*1G、CYP3A5*3、COMT Val158Met和OPRM1 A118G基因多态性与围术期芬太尼用量和视觉模拟评分法(VAS)评分之间的关系。方法选择2018年7月至2020年12月在复旦大学附属中山医院进行腹腔镜结肠肿瘤根治术的101例患者为研究对象。通过PCR扩增和Sanger测序检测CYP3A4*1G、CYP3A5*3、COMT Val158Met和OPRM1 A118G基因单核苷酸多态性,分析多个基因的单核苷酸多态性与围术期芬太尼用量、VAS评分之间的关系。结果101例患者中,CYP3A4*1G GG野生型50例(49.50%)、GA杂合子38例(37.62%)、AA纯合子13例(12.88%);CYP3A5*3 AA野生型12例(11.88%)、AG杂合子44例(43.56%)、GG纯合子45例(44.56%);OPRM1 A118G AA野生型2例(1.98%)、GA杂合子14例(13.86%)、GG纯合子85例(84.16%);COMT Val158Met GG野生型53例(52.48%)、GA杂合子43例(42.57%)、AA纯合子5例(4.95%),等位基因频率符合Hardy-Weinberg平衡。CYP3A4*1G、CYP3A5*3不同基因分型患者麻醉后复苏观察室(PACU)中的芬太尼用量差异有统计学意义(P<0.05),GG基因型患者消耗更多的芬太尼。患者出PACU时VAS评分与PACU、手术室的芬太尼用量及OPRM1 A118G基因型呈正相关(r=0.598、0.220、0.426,P<0.05)。多重线性回归分析显示OPRM1 A118G基因型和PACU芬太尼用量是出PACU时VAS评分的独立影响因素(P<0.05)。术后24 h和48 h VAS评分与CYP3A4*1G、CYP3A5*3、COMT Val158Met、OPRM1 A118G基因型无相关性(P>0.05)。结论CYP3A4*1G基因型与PACU芬太尼用量有一定相关性。OPRM1 A118G基因型和PACU芬太尼用量是出PACU时VAS评分的独立影响因素,OPRM1 A118G A基因携带者相比携带突变纯合子患者消耗更多芬太尼才能获得相似的麻醉效果。术后24 h和48 h VAS评分与CYP3A4*1G、CYP3A5*3、COMT Val158Met、OPRM1 A118G基因型无相关性。

Objective To investigate the relationships between the polymorphisms of CYP3A4*1G,CYP3A5*3,COMT Val158Met and OPRM1 A118G with the perioperative fentanyl dosage and the visual analogue scale(VAS)score in the patients with laparoscopic colorectal tumor radical operation.Methods A total of 101 patients with laparoscopic colon tumor radical operation in this hospital from July 2018 to December 2020 were selected as the study subjects.Single nucleotide polymorphisms of CYP3A4*1G,CYP3A5*3,COMT Val158Met and OPRM1 A118G were detected by PCR amplification and Sanger sequencing,and the relationships between single nucleotide polymorphisms of several genes and perioperative fentanyl dosage,VAS score were analyzed.Results Among 101 patients,there were 50 cases(49.50%)of CYP3A4*1G wild type,38 cases(37.62%)of GA heterozygous genotype and 13 cases(12.88%)of AA homozygous genotype.There were 12 cases(11.88%)of CYP3A5*3 wild type,44 cases(43.56%)of AG heterozygous genotype and 45 cases(44.56%)of GG homozygous genotype.There were 2 cases(1.98%)of OPRM1 A118G AA wild type,14 cases(13.86%)of GA heterozygous genotype and 85 cases(84.16%)of GG homozygous genotype.There were 53 cases(52.48%)of COMT Val158Met wild type,43 cases(42.57%)of GA heterozygous genotype and 5 cases(4.95%)of AA homozygous genotype,and the allele frequency conformed to the Hardy-Weinberg equilibrium.There was a statistically significant difference in the fentanyl dose in PACU among the patients with different genotypes of CYP3A4*1G and CYP3A5*3(P<0.05),while the patients with GG genotype consumed more fentanyl.The VAS score when the patients were out of PACU was positively correlated with the use amount of fentanyl in PACU and operating room,and OPRM1 A118G genotype(r=0.598,0.220,0.426,P<0.05).The multiple linear regression analysis showed that the OPRM1 A118G genotype and PACU fentanyl dosage were the independent influencing factors for the VAS score out of PACU(P<0.05).The VAS scores at postoperative 24,48 h had no correlation with CYP3A4*1G,CYP3A5*3,COMT Val158Met and OPRM1 A118G genotypes(P>0.05).Conclusion The CYP3A4*1G polymorphism has a certain correlation with the fentanyl dosage.The OPRM1 A118G genotype and fentanyl dosage in PACU are the independent influencing factors for the VAS score out of PACU.The carriers of the OPRM1 A118G A gene consumes more fentanyl than those carrying mutant homozygotes to achieve a similar anesthetic effect.The VAS scores at postoperative 24,48 h have no correlation with the genotypes of CYP3A4*1G,CYP3A5*3,COMT Val158Met and OPRM1 A118G.