Göktaş M T, Pepedil F, Karaca Ö, Kalkışım S, Cevik L, Gumus E, Guven G S, Babaoglu M O, Bozkurt A, Yasar U
Department of Pharmacology, Faculty of Medicine, Yildirim Beyazit University, Ankara, Turkey.
Eur Rev Med Pharmacol Sci. 2016 Jun;20(11):2460-7.
Losartan is a selective angiotensin II receptor type 1 blocker and a substrate of drug efflux transporter MDR1 (ABCB1). MDR1 shows inter-individual variations due to genetic polymorphisms. C3435T, G2677T and C1236T polymorphic alleles of the MDR1 gene encoding the transporter have been shown to alter the transport, bioavailability and efficacy of certain drugs. The purpose of this study was to investigate the relationship between genetic polymorphisms of MDR1 (C3435T, G2677T/A and C1236T) and response to the treatment in newly diagnosed hypertensive patients being treated with losartan.
A total of 74 newly diagnosed hypertension patients were included in the study. Genotyping was performed using PCR-RFLP. Systolic and diastolic mean blood pressure changes of the patients were expressed as a percentage (± SD). Blood pressure values prior to initiation of the treatment and subsequent measurements 6 weeks after starting the treatment were compared.
Regarding the C3435T polymorphism, a mean decrease of systolic blood pressure in individuals with CT or TT genotype (n= 55; 11.6% ± 9.7 mmHg) was significantly higher compared with that of the CC genotype (n = 19; 6.7% ± 9.6 mmHg, p = 0.03). No significant systolic blood pressure changes observed in G2677T/A and C1236T genotypes (p = 0.13 and 0.07, respectively). There was not any significant difference in diastolic blood pressure changes between pre- and post-treatment for any of the genotypes with C3435T, G2677T/A, or C1236T variations.
This study revealed that hypotensive response to losartan was significantly affected by the C3435T genetic polymorphism of MDR1 and hypertensive patients with MDR1 3435T allele may present a better response to losartan treatment.
氯沙坦是一种选择性1型血管紧张素II受体阻滞剂，也是药物外排转运体MDR1（ABCB1）的底物。MDR1因基因多态性而存在个体间差异。编码该转运体的MDR1基因的C3435T、G2677T和C1236T多态性等位基因已被证明会改变某些药物的转运、生物利用度和疗效。本研究的目的是调查MDR1基因多态性（C3435T、G2677T/A和C1236T）与新诊断的接受氯沙坦治疗的高血压患者治疗反应之间的关系。
本研究共纳入74例新诊断的高血压患者。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）进行基因分型。患者的收缩压和舒张压平均变化以百分比（±标准差）表示。比较治疗开始前的血压值与开始治疗6周后的后续测量值。
关于C3435T多态性，CT或TT基因型个体（n = 55；11.6%±9.7 mmHg）的收缩压平均下降幅度显著高于CC基因型个体（n = 19；6.7%±9.6 mmHg, p = 0.03）。在G2677T/A和C1236T基因型中未观察到显著的收缩压变化（分别为p = 0.13和0.07）。对于C3435T、G2677T/A或C1236T变异的任何基因型，治疗前后舒张压变化均无显著差异。
本研究表明，MDR1的C3435T基因多态性显著影响氯沙坦的降压反应，携带MDR1 3435T等位基因的高血压患者可能对氯沙坦治疗有更好的反应。
