基于单核苷酸多态性的阿片类镇痛药个体化用药研究  

Study on individualized use of opioid analgesics based on SNP polymorphism

作　　者：彭婷婷[1] 朱效涛 宋琳琳 刘健[1] 郑磊 杨静 PENG Tingting;ZHU Xiaotao;SONG Linlin;LIU Jian;ZHENG Lei;YANG Jing(Dept.of Pharmacy,the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250002,China;Dept.of Pharmacy,Shandong Medical College,Jinan 250002,China;Dept.of Pharmacy,Shandong Provincial Third Hospital,Jinan 250031,China;School of Medical and Pharmaceutical Science,Ocean University of China,Shandong Qingdao 266000,China)

机构地区：[1]山东中医药大学第二附属医院药学部,济南250002 [2]山东医学高等专科学校药学系,济南250002 [3]山东省立第三医院药学部,济南250031 [4]中国海洋大学医药学院,山东青岛266000

出　　处：《中国药房》2024年第24期3041-3045,共5页China Pharmacy

基　　金：山东省医药卫生科技发展计划项目(No.202213010928);山东省医学会临床科研专项资金课题(No.YXH2020ZX047);济南市科技计划(后补助)项目(No.202134016)。

摘　　要：目的探讨基因多态性与阿片类镇痛药的药物不良反应(ADR)及需求量的相关性,以期指导阿片类镇痛药的个体化用药。方法利用已有循证医学证据确定阿片类镇痛药药效及ADR相关基因位点,选取强相关的单核苷酸多态性(SNP)位点开展临床病例对照研究。研究组分为ADR评价组与药物需求量评价组,其中ADR评价组共纳入254例癌痛患者,根据使用阿片类镇痛药后是否出现ADR分为试验亚组(出现ADR)和对照亚组(未出现ADR),两亚组分别纳入126例和128例患者;药物需求量评价组共纳入120例癌痛患者,根据使用阿片类镇痛药日剂量不同分为试验亚组(相当于口服吗啡日剂量≥100mg)和对照亚组(相当于口服吗啡日剂量<100mg),各纳入60例患者。对纳入研究的患者采用荧光原位杂交法进行SNP位点检测,采用SPSS21.0软件和SNPStats工具对基因检测结果进行各亚组间比较和相关性分析,以评估所选SNP位点在临床真实病例中与阿片类镇痛药ADR及药物需求量的相关性。结果筛选出的强相关SNP位点有CYP2D6*10(rs1065852,C>T)、CYP3A5*3(rs776746,A>G)、ABCB1(rs1045642,C>T)及OPRM1(rs1799971,A>G)。基因检测结果显示,以上SNP位点等位基因分布频率均符合Hardy-Weinberg遗传平衡。相关性分析结果显示,ADR评价组中,试验亚组与对照亚组比较,OPRM1(rs1799971,A>G)AA型占比更高(P<0.05);药物需求量评价组中,试验亚组与对照亚组比较,ABCB1(rs1045642,C>T)CC+CT型占比更高(P<0.05)。结论OPRM1(rs1799971,A>G)AA型与使用羟考酮后发生的ADR具有相关性;ABCB1(rs1045642,C>T)CC+CT型患者的阿片类镇痛药需求量更高。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

关 键 词：阿片类镇痛药 单核苷酸多态性 基因多态性 个体化用药 药物不良反应 药物需求量 

分 类 号：R971[医药卫生—药品]