SLCO1B1 388A>G与521T>C基因多态性对不同中等强度他汀降脂疗效与安全性的影响  

Effect of SLCO1B1388A>G and 521T>C Gene Polymorphisms on the Lipid-Lowering Efficacy and Safety of Different Moderate-Intensity Statins

作　　者：李静[1,2,3] 陈雯雯[2,3] 袁圆 马丽娟 赵军[2,3] LI Jing;CHEN Wenwen;YUAN Yuan;MA Lijuan;ZHAO Jun(College of Pharmacy,Xinjiang Medical University,Urumqi 830054,China;Department of Pharmacy,State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia,The First Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China;Xinjiang Key Laboratory of Clinical Drug Research,Urumqi 830011,China)

机构地区：[1]新疆医科大学药学院,乌鲁木齐830054 [2]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,乌鲁木齐830011 [3]新疆药物临床研究重点实验室,乌鲁木齐830011

出　　处：《中国药学杂志》2025年第4期412-421,共10页Chinese Pharmaceutical Journal

基　　金：国家重点研发计划项目资助(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资助资助(SKL-HIDCA-2022-JZ3);“天山英才”医药卫生高层次人才培养计划资助(TSYC202301A051)。

摘　　要：目的 分析冠心病患者溶质载体有机阴离子转运蛋白家族1B1(SLCO1B1)基因rs2306283(388A>G)与rs4149056(521T>C)2个位点基因多态性分布频率,探讨其单核苷酸多态性对不同种类中等强度他汀降脂疗效与安全性的影响。方法 收集183例冠心病患者血样,采用PCR-荧光探针法检测SLCO1B1 rs2306283与rs4149056基因多态性,收集患者进行中等强度剂量的瑞舒伐他汀、阿托伐他汀以及其他类他汀治疗前后的血脂与血生化指标检测结果,记录甘油三酯(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)以及尿素氮(BUN)、血清肌酐(Scr)、肌酸激酶(CK)、丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、直接胆红素(DBIL)与间接胆红素(IBIL)等,并计算以上指标用药前后的变化值。分析SLCO1B1 rs2306283、rs4149056基因多态性与不同种类中等强度他汀降脂疗效与安全性的关系。结果 SLCO1B1 A388G各基因型分布频率在汉族患者与维吾尔族患者中有显著性差异(P<0.05)。SLCO1B1 388AG+GG型患者治疗后LDL-C降低差值较AA型更明显(P<0.05)。388GG型患者使用瑞舒伐他汀和其他类他汀后HDL-C水平明显高于阿托伐他汀(P<0.05)。SLCO1B1 521TT型患者经其他类他汀治疗后HDL-C水平明显高于阿托伐他汀(P<0.05),经阿托伐他汀治疗后TC水平下降值及LDL-C水平降低改变值则明显优于瑞舒伐他汀(均P<0.05)。SLCO1B1 388AG基因型患者经瑞舒伐他汀治疗后ALP水平明显低于其他类他汀(P<0.05)。388GG型患者经其他类他汀治疗后DBIL水平较之瑞舒伐他汀和阿托伐他汀治明显升高(P<0.05)。SLCO1B1 521TC型患者治疗后IBIL、CK及ALT差值均高于TT型(均P<0.05)。TT型患者经阿托伐他汀治疗后AST升高差值较其他类他汀明显偏低(P<0.05)。TC基因型患者经阿托伐他汀和瑞舒伐他汀治疗后DBIL明显低于其他类他汀(均P<0.05)。结论 SLCO1B1 388G等位基�OBJECTIVE To analyze the distribution frequency of rs2306283 and rs4149056 polymorphisms in the solute carrier organic anion transporter family 1B1(SLCO1B1)gene and investigate the effect of SLCO1B1 gene on the efficacy and safety of different moderate kinds of statins in patients with coronary heart disease(CHD).METHODS A total of 183 blood samples of patients with CHD were collected,and polymerase chain reaction-fluorescence probe technology was used to detect the polymorphism of SLCO1B1 gene.Blood lipid indicators and blood biochemical indexes before and after statin treatment(atorvastatin,rosuvastatin,other statins),such as triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and urea nitrogen(BUN),serum creatinine(Scr),creatine kinase(CK),alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),direct bilirubin(DBIL),indirect bilirubin(IBIL),et al,were recorded.The change values of TG,TC,LDL-C,HDL-C,et al,were calculated.The relationships between SLCO1B1 gene polymorphism and the efficacy and safety of different statins in CHD patients were analyzed.RESULTS There was significant difference between Han and Uyghur CHD patients in the distribution frequency of SLCO1B1 A388G genotypes.The difference in LDL-C was significantly increased in SLCO1B1388AG+GG patients compared with AA(P<0.05).The difference of LDL-C after treatment in 388AA type was significant(P>0.05),and the change of HDL-C in GG type patients treated with rosuvastatin was significantly higher than patients with atorvastatin(P<0.05).The changes of HDL-C in TT genotype patients with other statins were significantly higher than patients with atorvastatin(P<0.05),and the change values of TC and LDL-C in TT genotype patients with atorvastatin were significantly higher than those of the rosuvastatin group(all P<0.05).The ALP levels in SLCO1B1388AG genotype patients with rosuvastatin were significantly lower than the other statins(P<0.05),and the DBIL

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

分 类 号：R969[医药卫生—药理学]