The Role Of OATP1B1, MDR1and CHRNA1Gene Polymorphisms On The Efficacy Of Rocuronium

Objective:Individual variability may impact the clinical response of Rocuronium. We investigated whether polymorphisms in OATP1B1388A>G, OATP1B1521T>C, MDR13435C>T, MDR11236C>T and CHRNA1rs16862847A>G affect the efficacy of rocuronium in Chinese patients.Methods:207otorhinolaryngologic patients with ASA grade Ⅰ Ⅱ,aging18to59years, were scheduled for selective operation under total intravenous general anesthesia. Anesthesia induction scheme: intravenous injection with midazolam0.06mg/kg,sufentanil0.7μg/kg,propofol lmg/kg and rocuronium0.6mg/kg successively; Anesthesia maintenance scheme:target-controlled infusion(TCI) of propofol(at3～5μg/ml) and remifentanil(at3～6ng/ml). Monitoring the neuromuscular function during the whole period of anesthesia with TOF-Watch SX muscle relaxant monitoring, superaddition rocuronium0.15mg/kg when TOF returned to25%.Record the change of patients’ vital signs during the induction and anesthetic finishing.Record the onset time of rocuronium,the time when TOF returned to25%and90%.2ml vein blood was extracted from each volunteer, applying PCR-RFLP to OATP1B1, MDR1and CHRNA1genotype analysis. Demographic and clinical non-genetic data were collected.Results:①Frequency of OATP1B1388AA, AG and GG genotype were respectively10%,37%and53%in Chinese patients. Clinical duration of initial dose in OATP1B1388AG and GG genotype patients was longer than that in OATP1B1388AA genotype patients (p<0.05). Clinical duration of maintenance dose of rocuronium in OATP1B1388AG and GG genotype patients was longer than that of OATP1B1388AA genotype patients (p<0.05). The recovery time of rocuronium in OATP1B1388AG and GG genotype patients was longer than that of OATP1B1388AA genotype patients(p<0.05).②The frequency of OATP1B1521TT, TC and TT genotypes were respectively80%,18%and2%in Chinese patients. There were no statistical differences in onset time, duration of action, recovery time of rocuronium among different OATP1B1521T>C patients (P>0.05).③Frequency of MDR11236CC, CT and TT genotype were respectively13%,49.5%and37.5%in Chinese patients. Clinical duration of initial dose of rocuronium in MDR11236TT genotype patients was longer than those of MDR11236CC and CT genotype patients (P<0.05). Clinical duration of maintenance dose of rocuronium in MDR11236TT genotype patients was longer than those of MDR11236CC and CT genotype patients (P<0.05). The recovery time of rocuronium in MDR11236TT genotype patients was longer than CC and CT genotype patients(p<0.05).④The frequency of MDR13435CC, CT and TT genotypes were respectively41.5%,39%and19.5%in Chinese patients. There were no statistical differences in onset time, duration of action, recovery time of rocuronium among different MDR13435C>T patients (P>0.05).⑤The frequency of CHRNA1rs16862847AA, AG and GG genotypes were respectively91%,8%and1%in Chinese patients. For the low rate of CHRNA1rs16862847GG genotype, we analyzed the data of CHRNA1rs16862847AG and CHRNA1rs16862847GG as one group. The results showed that there were no significant difference (P>0.05) in onset time, clinical duration of action and recovery time of rocuronium among CHRNA1rs16862847A>G patients.Conclusions:We demonstrated the OATP1B1and MDR1gene mutation obviously impact the clinical action of rocuronium, indicating that the hereditary factor is one of the reasons contributing to the individual variation in neuromuscular blockade induced with rocuronium in patients.