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Correlation of P2RX7 gene rs1718125 polymorphism with postoperative fentanyl analgesia in patients with lung cancer.

ABSTRACT: The aim of this study was to investigate the association between purinergic receptor P2X7 (P2RX7) gene rs1718125 polymorphism and analgesic effect of fentanyl after surgery among patients with lung cancer in a Chinese Han population.A total of 238 patients with lung cancer who received resection were enrolled in our study. The genotype distributions of P2RX7 rs1718125 polymorphism were detected by polymerase chain reaction and direct sequencing. Postoperative analgesia was performed by patient-controlled intravenous analgesia, and the consumption of fentanyl was recorded. The postoperative pain was measured by visual analog scale (VAS). Differences in postoperative VAS score and postoperative fentanyl consumption for analgesia in different genotype groups were analyzed by analysis of variance assay.The frequencies of GG, GA, and AA genotypes were 46.22%, 44.96%, and 8.82%, respectively. After surgery, the postoperative VAS score of GA group was significantly high in the period of analepsia after general anesthesia and at 6?hours after surgery (P?=?.041 and P?=?.030, respectively), while AA group exhibited obviously high in the period of analepsia after general anesthesia (P?

SUBMITTER: Ma J

PROVIDER: S-EPMC6408006 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Correlation of P2RX7 gene rs1718125 polymorphism with postoperative fentanyl analgesia in patients with lung cancer.

Ma Jin J Li Wenyao W Chai Qing Q Tan Xiaohong X Zhang Kexian K

Medicine 20190201 7

The aim of this study was to investigate the association between purinergic receptor P2X7 (P2RX7) gene rs1718125 polymorphism and analgesic effect of fentanyl after surgery among patients with lung cancer in a Chinese Han population.A total of 238 patients with lung cancer who received resection were enrolled in our study. The genotype distributions of P2RX7 rs1718125 polymorphism were detected by polymerase chain reaction and direct sequencing. Postoperative analgesia was performed by patient-c ...[more]

PMID: 30762755

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Project description:Background:The clinical efficacy of fentanyl for pain control differs greatly across individuals. The purpose of this study was to investigate the impact of CYP3A4*1G polymorphism including wild-type homozygote (CYP3A4*1/*1, GG), mutant heterozygote (CYP3A4*1/*1G, GA), and mutant homozygote (CYP3A4*1G/*1G, AA) on fentanyl analgesia in Chinese patients undergoing hysteroscopy by the assessment of analgesia nociception index (ANI). Methods:A total of 200 gynecologic patients scheduled for elective hysteroscopy under general anesthesia at Peking University People's Hospital from May to December in 2017 were enrolled in this study. Venous blood was withdrawn for genotyping of CYP3A4*1G before operation. Fentanyl 1 ?g/kg was administered preoperatively followed by target-controlled infusion of propofol for induction and maintenance. Intraoperative analgesic efficacy of fentanyl was assessed by ANI monitoring at T0 (entering room), T1 (cervical dilation), T2 (start of cervical aspiration), and T3 (end of cervical aspiration) time points. The duration of propofol infusion and total dosage of propofol were recorded as well. Results:The patients were divided into three groups according to CYP3A4*1G polymorphism, including 143 in GG group, 47 in GA group, and 10 in AA group. There was no significant difference in clinical demographics among three groups. The frequency of CYP3A4*1G variant alleles accounted for 16.8% and the distribution of variant alleles was consistent with Hardy-Weinberg equilibrium. Using a multilevel model, ANI values at T1 (63.81 ± 19.61), T2 (63.63 ± 17.82), and T3 (65.68 ± 17.79) were significantly lower than that at T0 (77.16 ± 12.93) in the study population (F = 23.50, P < 0.001), suggesting that higher levels of pain at T1, T2, and T3 than T0. Patients with GG genotype showed significantly lower ANI than those with GA or AA genotypes during hysteroscopy under the same dose of fentanyl. Conclusion:CYP3A4*1G polymorphism associated with the analgesic efficacy of intraoperative fentanyl in the patients undergoing hysteroscopy under general anesthesia.

Project description:BACKGROUND: The P2X7 receptor is a member of the P2X family of adenosine 5'-triphosphate-gated cation channels. Several recent studies have demonstrated that this receptor is involved in mechanisms related to pain and inflammation. However, unknown is whether polymorphisms of the P2RX7 gene that encodes the human P2X7 receptor influence pain sensitivity and analgesic effects of opioids. The P2RX7 gene is known to be highly polymorphic. Thus, the present study examined associations between fentanyl sensitivity and polymorphisms in the P2RX7 gene in 355 Japanese patients who underwent painful orofacial cosmetic surgery. RESULTS: We first conducted linkage disequilibrium (LD) analyses for 55 reported single-nucleotide polymorphisms (SNPs) in the region within and around the P2RX7 gene using genomic samples from 100 patients. In our samples, 42 SNPs were polymorphic, and a total of five LD blocks with six Tag SNPs (rs2708092, rs1180012, rs1718125, rs208293, rs1718136, and rs7132846) were observed. Thus, we further analyzed associations between genotypes/haplotypes of these Tag SNPs and clinical data using a total of 355 samples. In the genotype-based association study, only the rs1718125 G>A SNP tended to be associated with higher pain scores on a visual analog scale 24 h after surgery (VAS24). The haplotype-based association study showed that subjects with homozygous haplotype No.3 (GTAAAC; estimated frequency: 15.0%) exhibited significantly higher cold pain sensitivity and lower analgesic effects of fentanyl for acute cold pain in the cold pressor test. Conversely, subjects who carried haplotype No.1 (ACGGAC; estimated frequency: 24.5%) tended to exhibit lower cold pain sensitivity and higher analgesic effects of fentanyl. Furthermore, subjects with homozygous haplotype No.2 (GCGGAC; estimated frequency: 22.9%) exhibited significantly lower VAS24 scores. CONCLUSIONS: Cold pain sensitivity and analgesic effects of fentanyl were related to the SNP and haplotypes of the P2RX7 gene. The patients with the rs1718125 G>A SNP tended to show higher VAS24 scores. Moreover, the combination of polymorphisms from the 5'-flanking region to exon 5 recessively affected cold pain sensitivity and analgesic effects of opioids for acute cold pain. The present findings shed light on the involvement of P2RX7 gene polymorphisms in naive cold pain sensitivity and analgesic effects of fentanyl.

Dataset Information

Correlation of P2RX7 gene rs1718125 polymorphism with postoperative fentanyl analgesia in patients with lung cancer.

Publications

Correlation of P2RX7 gene rs1718125 polymorphism with postoperative fentanyl analgesia in patients with lung cancer.

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