Effect Of CYP3A4 SNP Rs2242480 On The Fentanyl Consumption For Intravenous Patient-controlled Analgesia After Total Abdominal Hysterectomy In Chinese Han Population

Objective:Clinical investigations of postoperative intravenous patient-controlled analgesia (PCA) have indicated inter-individual differences in fentanyl consumption. Cytochrome P450 3A4 (CYP3A4) is the main metabolism enzyme of fentanyl and single nucleotide polymorphisms within the CYP3A4 gene may contribute to the variability of fentanyl analgesic efficacy. The aim of the current study was to investigate whether the most common genetic variation in Chinese, CYP3A4*1G (CYP3A4rs2242480), has an impact on the fentanyl consumption for intravenous PCA in Chinese Han women undergone abdominal total hysterectomy.Methods:After informed consent was obtained, 79 female patients (American Society of Anesthesiologist physical status I or II) scheduled to undergo elective abdominal total hysterectomy were enrolled in this study. All patients received combined spinal-epidural anesthesia with bupivacaine. Intravenous fentanyl PCA was provided postoperatively for satisfactory analgesia. The doses of fentanyl consumption were recorded for 2,4,24 and 48 hrs after the initiation of PCA postoperatively. Pain at rest and adverse effects were measured with rating scales. CYP3A4*1G was screened by means of direct sequencing, and further confirmed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).Results:Forty-six patients were GG homozygotes,27 patients were GA heterozygotes and 6 patients were AA homozygotes, respectively. The distribution of the CYP3A4*1G allele was consistent with Hardy-Weinberg equilibrium (P>0.05). The demographic data between patients with GG genotype and those with GA/AA genotypes were comparable. At 2hrs and 4hrs, the dose of fentanyl required for patients with GA/AA genotypes was 80.0 (45.0,112.5)μg and 120.0 (80,173.8)μg, respectively, which was significantly lower than that for GG homozygote (91.3 [80.0,125.0]μg and 169.0 [112.5,226.3]μg, respectively, P＜0.05). Although there was a trend of decreasing fentanyl consumption at 24hrs and 48hrs in patients with GA/AA genotypes, when compared with that in patients with GG homozygote, there was no statistical difference.Conclusion:The present study found that CYP3A4*1G has an impact on the analgesic effect of fentanyl in Chinese Han population. Further study including large samples to confirm the present findings is guaranteed.