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目的研究多药耐药基因1(multi-drug resistance gene1,MDR1)C3435T基因多态性与厄贝沙坦血药浓度及临床疗效的关系,为高血压的个体化治疗提供依据。方法于2015年9月至2016年7月随机选取就诊于佳木斯大学附属第一医院的未口服任何降压药物至少2周的原发性高血压患者94例作为研究对象。根据检测的基因型不同分为3组,A组44例(CC型),B组38例(CT型),C组12例(TT型)。分别记录3组患者的初始血压值,并嘱其口服厄贝沙坦片150 mg/d,1周后分别测定3组厄贝沙坦的血浆血药浓度,同时随访3组患者1个月后的收缩压及舒张压变化情况,比较3组之间厄贝沙坦的降压疗效。应用SPSS 17.0统计软件进行χ2检验或方差分析。结果 A组、B组、C组3组之间标准血药浓度分别为(97.09±54.82)、(91.45±65.35)和(157.50±34.57)ng·kg·ml-1·mg-1,差异有统计学意义(P<0.05);A组和B组标准血药浓度均明显低于C组,差异有统计学意义(P<0.05),A组与B组之间标准血药浓度无明显差异。A组显效10例,有效6例,无效28例,降压有效率为36.36%;B组显效6例,有效6例,无效26例,降压有效率31.58%;C组显效8例,有效2例,无效2例,降压有效率为83.33%,3组间降压疗效差异有统计学意义(χ2=12.857,P<0.01)。A、B组降压疗效明显低于C组,A组与B组之间厄贝沙坦降压疗效无明显差异。结论不同MDR1 C3435T基因型的高血压患者对厄贝沙坦片的耐药程度不同,以致厄贝沙坦降压疗效不同,从而为临床高血压的治疗提供个体化方案。
Objective To study the relationship between multidrug resistance gene 1 (MDR1) C3435T gene polymorphism and irbesartan plasma concentration and clinical efficacy in order to provide evidence for the individualized treatment of hypertension. Methods From September 2015 to July 2016, 94 patients with essential hypertension who had not taken any antihypertensive drugs for at least 2 weeks in the First Affiliated Hospital of Jiamusi University were enrolled in this study. According to the detected genotypes, there were 3 groups: 44 cases in group A (CC type), 38 cases in group B (CT type) and 12 cases in group C (TT type). The initial blood pressure values were recorded in 3 groups of patients respectively. Oral administration of irbesartan tablets was given 150 mg / d. After 1 week, the plasma concentrations of irbesartan in 3 groups were measured. One month later, Systolic blood pressure and diastolic blood pressure changes were compared between the three groups irbesartan antihypertensive efficacy. SPSS 17.0 statistical software for χ2 test or analysis of variance. Results The standard blood concentrations of the three groups in group A, group B and group C were (97.09 ± 54.82), (91.45 ± 65.35) and (157.50 ± 34.57) ng · kg · ml-1 · mg-1, (P <0.05). The standard blood concentration of group A and group B were significantly lower than that of group C (P <0.05), and there was no significant difference between group A and group B . In group A, 10 cases were markedly effective, 6 cases were effective, 28 cases were ineffective, and the effective rate was 36.36%. In group B, 6 cases were markedly effective, 6 cases effective, 26 cases ineffective and 31.58% effective in lowering blood pressure. 2 cases were ineffective in 2 cases, and the effective rate of hypotension was 83.33%. There was significant difference in antihypertensive efficacy between the three groups (χ2 = 12.857, P <0.01). A, B group was significantly lower antihypertensive effect than C group, A group and B group irbesartan antihypertensive effect no significant difference. Conclusion Different MDR1 C3435T genotypes have different levels of resistance to irbesartan tablets, resulting in different effects of irbesartan in lowering blood pressure, so as to provide individualized plans for the treatment of hypertension.