多SNP位点分析对于他汀类药物相关肌病风险的预测价值-现代医学

多SNP位点分析对于他汀类药物相关肌病风险的预测价值

单位：1. 北京市大兴区人民医院药剂科, 北京 102600;
2. 北京天坛医院药学部, 北京 100071

分类号：R595.3

出版年·卷·期（页码）：2022·50·第八期（1009-1014）

摘要：

目的：探究基于多个基因位点的单核苷酸多态性(SNP)对于他汀类药物诱发的肌病 (SIM)的预测价值。方法：选取2019年9月至2020年10月我院收治的接受他汀类药物治疗的原发性高脂血症患者350例。根据治疗后是否出现SIM分为SIM组和非SIM组，收集两组患者临床资料，于患者入院时抽取空腹静脉血2 ml，采用PCR基因扩增法测定SLCO1B1、APOE、CATM三个基因位点的单核苷酸多态性，采用多因素Logistics回归分析影响患者使用他汀类药物后出现SIM的危险因素；构建SIM的早期预测模型并对其预测效能进行评估。结果：经过3个月的治疗，350例患者共出现37例SIM，据此分组后对比临床资料显示，SIM组患者年龄、合并肾脏疾病比例、SLCO1B1基因rs4149065位点基因分型及CATM基因rs9806699位点基因分型与非SIM组差异有统计学意义(P＜0.05)；多因素Logistic回归分析显示，年龄越大(OR=3.763)、SLCO1B1基因rs4149065位点CC分型比例升高(OR=28.800)是SIM发生的独立危险因素(P＜0.05)；CATM基因rs9806699位点AA分型比例降低(OR=0.052)是SIM发生的独立保护性因素(P＜0.05)。基于SNP的模型预测SIM的c指数为0.933(95%CI:0.891～0.973)，校正曲线显示本模型预测SIM发生与内部验证的一致性较好。结论：SLCO1B1基因rs4149065位点和CATM基因rs9806699位点的基因多态性可能与SIM发病有关，检测上述两种基因的SNP有助于早期预测在使用他汀类药物过程中发生SIM风险。

Objective: To explore the predictive value of models based on single nucleotide polymorphisms (SNP) at multiple gene loci for statin-induced myopathy (SIM).Methods: From September 2019 to October 2020,350 patients with primary hyperlipidemia who were treated with statins in our hospital were selected.All patients were divided into SIM group and non-SIM group according to whether SIM appeared after treatment.The clinical data of the two groups of patients were collected 2 ml of fasting venous blood was collected when the patients were admitted to the hospital.PCR gene amplification method was used to determine the three gene loci of SLCO1B1,APOE,and CATM.For single nucleotide polymorphisms,multivariate logistic regression analysis was used to analyze the risk factors that affect patients with SIM after using statins;the early prediction model of SIM was constructed and its predictive efficacy was evaluated.Results: After 3 months of treatment,a total of 37 cases of SIM occurred in 350 patients.According to this grouping,comparison of clinical data showed that the age of patients in the SIM group,the proportion of renal diseases,the genotype of SLCO1B1 gene rs4149065 locus,and the CATM gene rs9806699 point genotyping were statistically different from that of the non-SIM group (P<0.05),respectively;multivariate logistic regression analysis showed that the older the age (OR=3.763),the higher the proportion of CC typing at the rs4149065 site of the SLCO1B1 gene (OR=28.800) were all independent risk factors for the occurrence of SIM (P<0.05);the CATM gene rs9806699 site,the decrease in the proportion of AA classification (OR=0.052) were independent protective factors for the occurrence of SIM (P<0.05).The SNP-based model predicts that the c index of SIM was 0.933(95%CI:0.891~0.973).The calibration curve showed that the model predicted the occurrence of SIM in good agreement with internal verification.Conclusion: The genetic polymorphisms at the rs4149065 locus of the SLCO1B1 gene and the rs9806699 locus of the CATM gene may be related to the occurrence of SIM.Detection of the SNPs of the two genes can help early predict the risk of SIM during the use of statins.

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