Relationship between genetic polymorphisms of drug efflux transporter MDR1 (ABCB1) and response to losartan in hypertension patients.

ABSTRACT

OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.