Study on individualized use of opioid analgesics based on SNP polymorphism
OBJECTIVE To investigate the correlation between gene polymorphisms and adverse drug reaction(ADR)and demands of opioids,aiming to guide personalized opioid analgesic therapy.METHODS The existing evidence-based medical data were adopted to identify gene loci related to the efficacy and ADR of opioid analgesics and select highly relevant single nucleotide polymorphism(SNP)for a clinical case-control study.The study cohort was divided into two evaluation groups:ADR assessment and drug demand assessment.The ADR assessment group included 254 cancer pain patients and was subdivided into the trial subgroup(with ADR)and the control subgroup(without ADR)based on the presence or absence of ADR following opioid usage;the two subgroups included 126 and 128 patients,respectively.The drug demand assessment group included a total of 120 cancer pain patients,who were divided into trial subgroup(equivalent to a daily dose of oral morphine ≥100 mg)and control subgroup(equivalent to a daily dose of oral morphine＜100 mg)based on the different daily doses of opioid analgesics,with 60 patients in each subgroup.Polymorphism detection of SNP loci in these patients was performed using fluorescence in situ hybridization.SPSS 21.0 software and SNPStats genetic models were employed to compare genetic testing results between subgroups and conduct correlation analyses,aiming to evaluate the association of the selected SNP loci with opioid ADR and drug demand in clinical real-world cases.RESULTS The strongly correlated SNP loci identified were CYP2D6*10(rs1065852,C＞T),CYP3A5*3(rs776746,A＞G),ABCB1(rs1045642,C＞T)and OPRM1(rs1799971,A＞G).Genetic testing results indicated that the allele frequency distributions of these SNP loci conformed to Hardy-Weinberg equilibrium.Correlation analysis revealed that in the ADR assessment group,compared with control subgroup,the proportion of patients in trial subgroup with the AA genotype of OPRM1(rs1799971,A＞G)was significantly higher(P＜0.05);in the drug demand assessment group,compared with control subgroup,the proportion of patients in trial subgroup with the CC+CT genotype of ABCB1(rs1045642,C＞T)was significantly higher(P＜0.05).CONCLUSIONS The AA genotype of OPRM1(rs1799971,A＞G)is associated with the occurrence of ADR following oxycodone use.Patients with the CC+CT genotype of ABCB1(rs1045642,C＞T)require higher doses of opioid analgesics.
万方数据
维普
