SLCO1B1和ApoE基因多态性对不同种类中等强度剂量他汀降脂疗效的影响  

Effects of SLCO1B1 and ApoE gene polymorphisms on the lipid-lowering efficacy of different types of moderate-intensity doses of statins

作　　者：李静[1] 袁圆[1] 马丽娟[1] 阮洁 王建华[1] 赵军[1] LI Jing;YUAN Yuan;MA Li-juan;RUAN Jie;WANG Jian-hua;ZHAO Jun(Department of Pharmacy,State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia,The First Affliated Hospital of Xinjiang Medical University,Urumqi 830011,Xinjiang Uygur Autonomous Region,China)

机构地区：[1]新疆医科大学第一附属医院药学部,省部共建中亚高发病成因与防治国家重点实验室,新疆维吾尔自治区乌鲁木齐830011

出　　处：《中国临床药理学杂志》2023年第18期2626-2630,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家重点研发计划课题基金资助项目(2017YFC0910001);省部共建中亚高发病成因与防治国家重点实验室开放课题基金资助项目(SKL-HIDCA-2022-JZ3)。

摘　　要：目的 研究溶质载体有机阴离子转运蛋白家族1B1(SLCO1B1)基因rs2306283、rs4149056及载脂蛋白E(ApoE)基因rs429358、rs7412遗传多态性对不同种类中等强度他汀降脂疗效的影响。方法 收集冠心病患者血样,用聚合酶链反应-荧光探针法检测SLCO1B1、ApoE基因多态性,记录治疗前后三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C),并计算其变化差值,分析SLCO1B1、ApoE基因多态性与不同种类中等强度他汀降脂疗效的关系。结果 本研究纳入231例冠心病患者。SLCO1B1 rs2306283 AG型在汉族与维吾尔族患者中分布频率分别为37.50%和50.67%,GG型分别为53.91%和34.66%(均P<0.05);ApoE rs429358 CC型在男性与女性患者中分布频率分别为0%和4.92%(P<0.05)。SLCO1B1 rs2306283 GG型患者经阿托伐他汀治疗后的HDL-C为(0.91±0.27)mmol·L^(-1)均显著低于瑞舒伐他汀(1.13±0.38)mmol·L^(-1)与其他类他汀(1.13±0.42)mmol·L^(-1)(均P<0.05)。SLCO1B1 rs4149056 TT型患者经其他类他汀治疗后的HDL-C为(1.10±0.34)mmol·L^(-1)显著高于阿托伐他汀(0.90±0.28)mmol·L^(-1)(P<0.01);经阿托伐他汀治疗后LDL-C下降值为(-0.50±0.76)mmol·L^(-1)显著优于瑞舒伐他汀(-0.13±0.84)mmol·L^(-1)(P<0.05)。ApoE rs429358 TT型患者经阿托伐他汀治疗后TC差值和LDL-C差值分别为(-0.71±1.02)mmol·L^(-1)与(-0.54±0.79)mmol·L^(-1),均优于瑞舒伐他汀(均P<0.05)。ApoE rs7412 CC型患者经瑞舒伐他汀和其他类他汀治疗后的HDL-C分别为(1.02±0.34)和(1.11±0.34)mmol·L^(-1)均高于阿托伐他汀(0.89±0.26)mmol·L^(-1)(均P<0.05)。结论 SLCO1B1和ApoE基因多态性对中等强度阿托伐他汀、瑞舒伐他汀降脂疗效有一定的影响,可能作为预测他汀降脂疗效的遗传学指标。Objective To investigate the effect of rs2306283 and rs4149056 polymorphisms of organic anion transporter family 1B1(SLCO1B1)gene and rs429358,rs7412 polymorphism of apolipoprotein E(ApoE)gene on the lipid-lowering efficacy of different moderate intensity statins.Methods The blood samples of patients with coronary heart disease were collected,polymerase chain reaction-fluorescence probe technology was used to detect the polymorphism of SLCO1B1 and ApoE gene.Blood lipid indicators before and after moderate intensity statins treatment,such as triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were recorded,and the change value of TG,TC,LDL-C,HDL-C were calculated.The relationship between SLCO1B1 and ApoE gene polymorphism and lipid-lowering efficacy of different kinds of moderate-intensity statins was analyzed.Results A total of 231 patients with coonary heart disease were enrolled in this study.The distribution frequency of SLCO1B1 rs2306283AG genotype were 37.50%and 50.67%,and GG genotype were 53.91%and 34.66%in Han and Uyghur patients,with statistically significant difference between the two group(all P<0.05).The distribution frequency of ApoE rs429358 CC genotype were 0%and 4.92%in male and female patients with statistically significant difference(P<0.05).The HDL-C after treatment in SLCO1B1 rs2306283 GG genotype was atorvastatin(0.91±0.27)mmol L^(-1) lower than rosuvastatin(1.13±0.38)and other statins(1.13±0.42)mmol L^(-1)(P<0.05).The HDL-C after treatment in SLCO1B1 rs4149056 TT genotype was other statins(1.10±0.34)mmol L-apparently higher than atorvastatin(0.90±0.28)mmol L^(-1)(P<0.01),and the drop value of LDL-C after treatment was atorvastatin(-0.50±0.76)mmol L^(-1)better than rosuvastatin(-0.13±0.84)mmol L^(-1)(P<0.05).The drop value of TC(-0.71±1.02)mmol L^(-1)and LDL-C(-0.54±0.79)mmol L-after atorvastatin treatment in type ApoE rs429358 TT were better than rosuvastatin(all P<0.05).The HDL-C after treatment in ApoE rs74

关 键 词：溶质载体有机阴离子转运蛋白家族1B1 载脂蛋白E 基因多态性 中等强度他汀 疗效 

分 类 号：R972.6[医药卫生—药品]