他汀类药物代谢相关基因检测在心脑血管疾病个体化用药中的作用  

Role of the determination of statin metabolism-related gene in the treatment of cardiovascular and cerebrovascular diseases

作　　者：童明宏[1] 丁慧[1] 蒋银婷 孙寒晓[1] 宣彬彬[1] 盛慧明[1] TONG Minghong;DING Hui;JIANG Yinting;SUN Hanxiao;XUAN Binbin;SHENG Huiming(Tongren Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200336, China;Jiangsu University,Zhenjiang 212013,Jiangsu,China)

机构地区：[1]上海交通大学医学院附属同仁医院,上海200336 [2]江苏大学,江苏镇江212013

出　　处：《检验医学》2019年第6期491-497,共7页Laboratory Medicine

基　　金：上海市长宁区科学技术委员会资助项目(CNKW2013J09);上海交通大学医学院附属同仁医院重点P(TR2017xk10)

摘　　要：目的探讨他汀类药物代谢相关基因检测在心脑血管疾病患者个体化用药及血脂管理中的作用。方法选取141例心脑血管疾病患者(冠心病72例、脑梗死69例)及70名体检健康者(正常对照组)。检测所有对象血清载脂蛋白A(apo A)、载脂蛋白B(apo B)、载脂蛋白E(apo E)、脂蛋白(a)[Lp(a)]、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、游离脂肪酸(FFA)水平,同时检测他汀类药物代谢相关基因ABCB1(2677G>T)、ABCB1(3435C>T)和SLCO1B1*5(T>C)单核苷酸多态性(SNP)。在72例冠心病患者中选取41例进行他汀类药物治疗前后基因多态性与血脂水平的相关性分析。结果心脑血管疾病组血清TG、HDL-C、apo A、Lp(a)、FFA水平与正常对照组比较,差异均有统计学意义(P<0.05);冠心病组血清TG、HDL-C、LDL-C、apo A、Lp(a)、FFA水平与正常对照组比较,差异均有统计学意义(P<0.05);脑梗死组血清TG、HDL-C、Lp(a)水平与正常对照组比较,差异均有统计学意义(P<0.05);其他血脂项目各组间比较差异均无统计学意义(P>0.05)。心脑血管疾病组、脑梗死组、冠心病组的基因分型和基因频率分布一致,均为ABCB1(2677G>T)G等位基因频率高于T等位基因频率、ABCB1(3435C>T)C等位基因频率高于T等位基因频率、SLCO1B1*5(T>C)T等位基因频率高于C等位基因频率。41例冠心病患者采用他汀类药物治疗后,血清TG、TC、LDL-C水平明显低于治疗前(P<0.05),血清HDL-C水平明显高于治疗前(P<0.05)。不同基因型患者对他汀类药物的疗效存在明显差异(P<0.05)。结论心脑血管疾病患者血脂水平异常,同一疾病患者的基因多态性存在明显的个体差异。心脑血管疾病患者的药物基因组学检测对指导他汀类药物临床降脂治疗有重要作用。Objective To study the individualized application of statin metabolism-related genomics in patients with cardiovascular and cerebrovascular diseases,and to investigate its role in blood lipid management. Methods A total of 141 patients with cardiovascular and cerebrovascular diseases(72 cases of coronary heart disease and 69 cases of cerebral infarction) were enrolled,and 70 healthy subjects were enrolled as healthy control group. Serum apolipoprotein A(apo A),apolipoprotein B(apo B),apolipoprotein E(apo E),lipoprotein(a)[Lp(a)],total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol (HDL-C),free fatty acid(FFA) and the statin gene ABCB1(2677G>T),ABCB1(3435C>T)and SLCO1B1*5(T>C)single nucleotide polymorphisms(SNP) were determined. Results Serum TG,HDL-C,apo A,Lp(a) and FFA levels in cardiovascular and cerebrovascular disease group had statistical significance compared with healthy control group(P<0.05). Serum TG,HDL-C,LDL-C,apo A,Lp(a) and FFA levels in coronary heart disease group had statistical significance compared with healthy control group(P<0.05). Serum TG,HDL-C and Lp(a) levels in cerebral infarction group had statistical significance compared with healthy control group(P<0.05). Other blood lipid indicators had no statistical significance(P>0.05). The genotypes and frequency distributions of cardiovascular and cerebrovascular disease group,cerebral infarction group and coronary heart disease group had consistency. ABCB1(2677G>T) G allele frequency was higher than T allele frequency,ABCB1(3435C>T) C allele frequency was higher than T allele frequency,and SLCO1B1*5(T>C) T allele frequency was higher than C allele frequency. After the treatment with statins,serum TG,TC and LDL-C levels were lower than those before treatment(P<0.05),and serum HDL-C level was higher than that before treatment(P<0.05). There was statistical significance in the efficiency of statins in patients with different genotypes(P<0.05). Conclusions There are abnormal blood li

关 键 词：他汀类药物 基因组学 单核苷酸多态性 冠心病 脑梗死 

分 类 号：R446.1[医药卫生—诊断学]