ABCB1 G2677T基因多态性检测在缺血性脑卒中患者应用阿托伐他汀降脂治疗中的价值

Value of ABCB1 G2677T gene polymorphism detection in lipid-lowering therapy with atorvastatin in patients suffered from ischemic stroke

目的:探讨三磷酸腺苷结合盒转运体B1(ABCB1)G2677T基因多态性检测在缺血性脑卒中患者应用阿托伐他汀降脂治疗中的价值。方法:本研究为前瞻性研究。连续招募116例缺血性脑卒中患者作为受试者,采用荧光染色原位杂交技术检测受试者ABCB1 G2677T(rs2032582)基因多态性,依据基因检测结果将患者分为GG基因型、GT基因型和TT基因型三组。三组患者均给予阿托伐他汀20 mg/d降脂治疗,重复测量资料方差分析比较治疗前及治疗1个月后三组受试者血清高密度脂蛋白(high density lipoprotein cholesterol,HDL-C)、低密度脂蛋白(low density lipoprotein cholesterol,LDL-C)、总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)水平的变化,以血清LDL-C水平<1.8 mmol/L为降脂治疗有效,比较三组治疗有效率的差异。记录三组药品不良反应发生情况。结果:GG基因型、GT基因型和TT基因型三组分别有47例(40.5%)、43例(37.1%)和26例(22.4%)患者。治疗前,三组血清TC、TG、HDL-C、LDL-C水平差异无统计学意义(均P>0.05)。治疗后,三组血清TC、TG、LDL-C水平均低于治疗前,HDL-C水平高于治疗前,且有随治疗时间变化的趋势(F_(TC)=77.780,P<0.001;F_(TG)=14.218,P<0.001;F_(LDL-C)=105.106,P<0.001;F_(HDL-C)=6.811,P=0.010);ABCB1 G2677T不同基因类型与治疗时间(血清LDL-C)有交互作用(F=3.604,P=0.030),三组血清LDL-C水平随时间的变化趋势不同;ABCB1 G2677T不同基因类型与治疗时间(血清TC、TG、HDL-C)无交互作用(F_(TC)=2.545,P=0.083;F_(TG)=0.585,P=0.559;F_(HDL-C)=0.012,P=0.988),三组血清TC、TG、HDL-C水平随时间的变化趋势相同。GG基因型组血清LDL-C水平下降幅度为36.99%(16.03%,50.13%),高于GT基因型组的22.75%(12.43%,41.11%)和TT基因型组的16.66%(7.37%,24.82%),三组血清LDL-C水平下降幅度差异有统计学意义(χ^(2)=11.630,P=0.003),且GG基因型组下降幅度显著高于TT基因型组(P=0.002)。GG基因型组降脂治疗有效率为72.34%,高于GT基因型组的44.18%和TT基因型组的38.46%,三组有效率差异有统计学意义(χ^(2)=10.565,P=0.005),且GG基因型组有效率显著高于TT组(χ^(2)=8.024,P=0.005)。三组药品不良反应总发生率相近(χ^(2)=1.649,P=0.438)。结论:ABCB1 G2677T基因GG基因型患者降脂幅度及降脂有效率均高于GT基因型和TT基因型,检测ABCB1 G2677T基因多态性在缺血性脑卒中患者应用阿托伐他汀降脂治疗中有一定应用价值。

AIM:To explore the value of adenosine triphosphate-binding cassette transporter B1(ABCB1)G2677T gene polymorphism detection in lipid-lowering therapy with atorvastatin in patients suffered from ischemic stroke.METHODS:This study was a prospective study.116 patients with ischemic stroke were recruited consecutively as subjects.The ABCB1 G2677T(rs2032582)gene polymorphism was detected by fluorescence staining in situ hybridization.According to the detection results,the patients were divided into GG genotype,GT genotype and TT genotype groups.All patients in the three groups were given atorvastatin 20 mg/d for lipid-lowering treatment.The changes of serum HDL-C,LDL-C,TC and TG levels in the three groups before and after treatment were compared by repeated measures analysis of variance.The serum LDL-C level<1.8 mmol/L was considered as the effective treatment for lowering blood lipid,and the difference of effective rate among the three groups was compared.The adverse drug reactions of the three groups were recorded.RESULTS:There were 47(40.5%),43(37.1%)and 26(22.4%)patients in GG genotype,GT genotype and TT genotype groups,respectively.There was no significant difference in serum TC,TG,HDL-C and LDL-C levels among the three groups before treatment(P>0.05);After treatment,the levels of serum TC,TG and LDLC in the three groups were lower than those before treatment,and the levels of HDL-C were higher than those before treatment,and there was a trend of change with treatment time(F_(TC)=77.780,P<0.001;F_(TG)=14.218,P<0.001;F_(LDL-C)=105.106,P<0.001;F_(HDL-C)=6.811,P=0.010);The interaction existed between different gene types of ABCB1G2677T and treatment time in serum LDL-C(F=3.604,P=0.030),and the change trend of serum LDL-C level with time was different in the three groups;There was no interaction between different gene types of ABCB1 and treatment time inserum TC,TG,HDL-C(F_(TC)=2.545,P=0.083;F_(TG)=0.585,P=0.559;F_(HDL-C)=0.012,P=0.988),and the change trend of serum TC,TG,HDLC levels with time was the same in the three groups.The decrease of serum LDL-C level in GG genotype group was 36.99%(16.03%,50.13%),which was higher than 22.75%(12.43%,41.11%)in GT genotype group and 16.66%(7.37%,24.82%)in TT genotype group.The difference in the decrease of serum LDL-C level among the three groups was statistically significant(χ^(2)=11.630,P=0.003),and the decrease in GG genotype group was significantly higher than that in TT genotype group(P=0.002).The effective rate of lipid-lowering treatment in GG genotype group was 72.34%,higher than 44.18%in GT genotype group and 38.46%in TT genotype group.There was a statistically significant difference in the effective rate among the three groups(χ^(2)=10.565,P=0.005),and the effective rate in GG genotype group was significantly higher than that in TT genotype group(χ^(2)=8.024,P=0.005).The total incidence of adverse drug reactions in the three groups was similar(χ^(2)=1.649,P=0.438).CONCLUSION:The blood lipid lowering extent and effective rate of GG genotype patients with ABCB1 G2677T gene are higher than those of GT genotype and TT genotype patients.Detection of ABCB1 G2677T gene polymorphism has certain application value in the treatment of ischemic stroke patients with atorvastatin.