摘要
目的分析载脂蛋白E(ApoE)与溶质载体有机阴离子转运蛋白家族1B1(SLCO1B1)基因多态性与他汀类药物降脂疗效的关系,为实现他汀类药物的精准用药提供参考依据。方法选择初诊需服用他汀类药物降脂治疗的300例心血管疾病患者,均于入组时检测血脂指标及ApoE、SLCO1B1基因多态性,并采用随机数字表法分为常规组和个体化组,每组150例。常规组患者按常规剂量给予他汀类药物治疗,个体化组患者给予个体化他汀类药物治疗(根据ApoE、SLCO1B1基因型调整他汀类药物种类和剂量)。比较两组ApoE、SLCO1B1基因型分布情况,治疗前后血脂指标[甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)]、肝功能指标[天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)]、肌酸激酶(CK)水平,治疗后血脂达标率及达标时间,不良反应发生情况。结果300例患者中ApoE基因型中保护类基因型63例,占21.00%;大众类基因型173例,占57.67%;风险类基因型64例,占21.33%。SLCO1B1基因型中低风险基因型190例,占63.33%;中等风险基因型83例,占27.67%;高风险基因型27例,占9.00%。两组患者ApoE基因型、SLCO1B1基因型分布比较差异均无统计学意义(P>0.05)。治疗后,两组TG、TC、LDL-C水平均低于本组治疗前,HDL-C水平高于本组治疗前,差异有统计学意义(P<0.05);个体化组TG、TC、LDL-C水平分别为(1.86±0.18)、(5.30±0.43)、(3.45±0.36)mmol/L,均低于常规组的(2.38±0.29)、(5.52±0.49)、(3.61±0.38)mmol/L,差异有统计学意义(P<0.05);两组HDL-C水平比较差异无统计学意义(P>0.05)。个体化组治疗后血脂达标率为97.33%,高于常规组的70.67%,差异有统计学意义(P<0.05);个体化组血脂达标患者达标时间为(22.40±2.81)d,短于常规组的(26.72±3.86)d,差异有统计学意义(P<0.05)。个体化组不良反应发生率为3.33%,常规组为4.00%,比较差异无统计学意义(P>0.05)。两组治疗前后AST、ALT、CK水平组间及组内比较差异无统计学意义(P>0.05)。结论广西地区人群的ApoE、SLCO1B1基因型分布与国内分布基本一致。根据ApoE、SLCO1B1基因多态性指导他汀类药物的降脂治疗可提高降脂疗效,且ApoE、SLCO1B1基因多态性可作为心血管疾病患者他汀类药物降脂疗效预测的辅助指标。
Objective To analyze the correlation of apolipoprotein E(ApoE)and solute carrier organic anion transporterfamily member 1 B1(SLCO1B1)gene polymorphisms with lipid-lowering efficacy of statins,so as to provide reference for the precision use of statins.Methods A total of 300 patients with cardiovascular and cerebrovascular diseases who were initially diagnosed and required lipid-lowering treatment with statins were selected.At the time of enrollment,all patients were tested for blood lipid indicators and ApoE and SLCO1B1 gene polymorphisms.They were divided into a conventional group and an individualized group using a random number table method,with 150 cases in each group.The conventional group received standard-dose statin treatment,while the individualized group received personalized statin treatment(adjusting the type and dosage of medication based on ApoE and SLCO1B1 genotypes).Comparison was made on distribution of ApoE and SLCO1B1 genotypes,blood lipid indicators[triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)],liver function indicators[aspartate transaminase(AST),alanine aminotrasferase(ALT)]and creatine kinase(CK)levels before and after treatment,rate of reaching lipid targets and time to reach lipid targets after treatment,and occurrence of adverse reactions between the two groups.Results Among the 300 patients,there were 63 cases(21.00%)with protective ApoE genotypes,173 cases(57.67%)with common genotypes,and 64 cases(21.33%)with risk genotypes.For SLCO1B1 genotypes,there were 190 cases(63.33%)with low-risk genotypes,83 cases(27.33%)with medium-risk genotypes,and 27 cases(9.00%)with high-risk genotypes.The differences in the distribution of ApoE genotypes and SLCO1B1 genotypes between the two groups of patients were not statistically significant(P>0.05).After treatment,the levels of TG,TC,and LDL-C in both groups were lower than those before treatment in this group,and the HDL-C level was higher than that before treatment in this group.The difference was statistically significant(P<0.05).The levels of TG,TC,and LDL-C were(1.86±0.18),(5.30±0.43),and(3.45±0.36)mmol/L in the individualized group,which were lower than(2.38±0.29),(5.52±0.49),and(3.61±0.38)mmol/L in the conventional group,and the difference was statistically significant(P<0.05).There was no statistically significant difference in HDL-C level between the two groups(P>0.05).After treatment,the rate of reaching lipid targets was 97.33%in the individualized group,which was higher than 70.67%in the conventional group,and the difference was statistically significant(P<0.05).The time to reach lipid targets was(22.40±2.81)d in the individualization group,which was shorter than(26.72±3.86)d in the conventional group,and the difference was statistically significant(P<0.05).The incidence rate of adverse reactions was 3.33%in the individualized group and 4.00%in the conventional group,and the difference was not statistically significant in comparison(P>0.05).There was no statistically significant difference in the comparison of AST,ALT and CK levels between and within the two groups before and after treatment(P>0.05).Conclusion The distribution of ApoE and SLCO1B1 genotypes in Guangxi region is basically consistent with the domestic distribution.Guided by ApoE and SLCO1B1 gene polymorphisms.The lipid-lowering treatment of statins guided by ApoE and SLCO1B1 gene polymorphisms can improve the lipid-lowering effect,and ApoE and SLCO1B1 gene polymorphisms can be used as auxiliary indexes to predict the lipid-lowering effect of statins in patients with cardiovascular diseases.
作者
黎华
殷君
杨云飞
庞柳英
韩晓静
罗淋尹
农洁偶
卢秋杰
何本进
何凤珍
黄盼柳
周红
黎静
LI Hua;YIN Jun;YANG Yun-fei(Department of Clinical Laboratory,Jiangbin Hospital of Guangxi Zhuang Autonomous Region,Nanning 530021,China)
出处
《中国实用医药》
2024年第23期1-6,共6页
China Practical Medicine
基金
自治区卫生健康委自筹经费科研课题(项目编号:Z-A20230226、Z-A20240215、Z-A20230270)项目名称:ApoE、SLCO1B1基因多态性与他汀降脂疗效的相关性研究。
