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

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 rs7412 CC genotype were rosuvastatin(1.02±0.34)mmol L^(-1) and other statins(1.11±0.34)mmol L^(-1) higher than atorvastatin(0.89±0.26)mmol L^(-1)(all P<0.05).Conclusion SLCO1B1 and ApoE gene polymorphisms have some effects on the lipid-lowering efficacy of moderate-intensity atorvastatin and rosuvastatin,which may be a genetic indicator to predict the efficacy of statins.