心房颤动患者ABCB1基因多态性与达比加群酯临床疗效的关系

目的探索维吾尔族(维族)心房颤动患者ABCA1基因C3435T位点多态性与达比加群酯治疗效果的关系。方法选取2015年1月至2016年12月在新疆医科大学第五附属医院住院或门诊就诊的维族、汉族心房颤动患者166例作为研究对象。检测入选患者的ABCA1基因C3435T位点多态性,再分别检测并比较不同基因型患者达比加群酯治疗后的血药浓度、凝血指标和出血事件。结果维族患者共73例,C3435T位点CC、CT、TT基因型分别占31.5%、49.3%、19.2%,C和T等位基因分别占56.2%、43.8%,与汉族患者在该位点的基因型和等位基因频率比较,差异无统计学意义(P>0.05)。达比加群酯治疗后,TT组患者的血药峰浓度和谷浓度最高,分别为(242.48±40.04)mg/L和(42.15±7.74)mg/L,CT型组次之,CC型组最低,且差异具有统计学意义(P<0.001)。服用达比加群酯4 d后,患者凝血指标发生显著性变化(P<0.01),其中TT型组活化部分凝血酶时间(APTT)显著高于CT型组(39.43±5.09)s vs.(34.21±4.92)s,P<0.01]和CC型组(39.43±5.09)s vs.(33.91±4.07)s,P<0.01],差异有统计学意义,治疗前后变化率为0.33±0.17;TT型组凝血酶时间(TT)显著高于CC型组(P<0.01),与TC型组比较,差异无统计学意义(P>0.05),治疗前后变化率达4.55±2.85;而凝血酶原时间(PT)、凝血酶原时间变化率、国际标准化比值(INR)和国际标准化比值变化率在不同基因型患者中比较,差异无统计学意义(P>0.05)。不同基因型的心房颤动患者在达比加群酯治疗期间的出血事件发生率比较,差异无统计学意义(P>0.05)。结论维族和汉族ABCB1基因C3435T基因型和基因频率均无显著性差异。C3435T多态性影响维族心房颤动患者口服达比加群酯后的血药浓度和凝血指标,但不影响出血事件。

Correlation between ABCB1 gene polymorphism and clinical efficacy of Pradaxa in patients with atrial fibrillation

Objectives To explore the correlation between ABCA1 gene C3435 T polymorphism and the therapeutic effect of pradaxa in Xinjiang Uygur patients with atrial fibrillation.Methods Totally 166 patients with atrial fibrillation in Uygur and Han nationalities were studied from January 2015 to December 2016 in The Fifth Affiliated Hospital of Xinjiang Medical University.The polymorphism of C3435 T locus of ABCA1 gene was detected.The blood concentration,coagulation index and hemorrhagic events of patients with different genotypes after treatment with pradaxa were detected respectively.Results There were 73 Uygur patients were detected.The genotypes of CC,CT and TT at C3435 T locus accounted for 31.5%,49.3%and 19.2%respectively.The C and T alleles accounted for 56.2%and 43.8%respectively.There were no significant differences in genotype and allele frequencies at this locus between Han and Uygur patients.After taken pradaxa,the peak and trough concentrations of drugs in blood of patients with TT type(242.48±40.04)mg/L and(42.15±7.74)mg/L respectively]are significantly higher than those of patients with CT and CC types(P<0.001).Coagulation index changed significantly after patients taking pradaxa for 4 days(P<0.01).The activated partial thrombin time(APTT)of patients with TT type was significantly higher than those of patients with CT type(39.43±5.09)s vs.(34.21±4.92)s,P<0.01]and CC type(39.43±5.09)s vs.(33.91±4.07)s,P<0.01],and average rate of change after treatment was 0.33±0.17.The thrombin time(TT)of TT type was significantly higher than CC type(P<0.01),but there was no statistical difference with TC type(P>0.05),and average rate of change after treatment was 4.55±2.85.While prothrombin time(PT),PT change rate,international standardized ratio(INR)and INR change rate among different genotypes were not significant different.The incidences of hemorrhagic events during the treatment of pradaxa were not significant different between different gene types.Conclusions There was no significant difference in genotype and frequency of ABCB1 gene C3435 T polymorphism between Uygur and Han nationalities.C3435 T polymorphism affects the blood concentration and coagulation index after patients taking pradaxa,but it does not affect the bleeding events.