International Journal of Clinical Pharmacology and Therapeutics · 2016 · 32 citations · 0 references
MedicinePharmacokineticsPharmacologyKidney TransplantationPharmacogeneticsPharmacogenomicsPharmacogenetic TestingPharmacogenomics In TransplantationAntihypertensive PharmacogenomicsAntihypertensive TreatmentBlood Pressure PharmacodynamicsCyp3a4 Genetic VariationCyp3a5 PharmacogeneticsCytochrome P450 Genetic PolymorphismCytochrome P450 Genotype EffectsGenetic Polymorphisms
OBJECTIVE: Blood samples were collected from 76 patients on amlodipine therapy (5 mg/d). METHODS: The CYP3A4*1G, CYP3A5*3, and MDR1 C3435T genetic polymorphisms were detected using both polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and gene sequencing. Subsequently, antihypertensive effects were analyzed according to genotype, and blood pressure values were measured and recorded weekly. RESULTS: Four weeks of treatment with amlodipine was sufficient to successfully control blood pressure in 79% of patients. The efficacy of amlodipine in patients with the CYP3A5*3*3 genotype was significantly higher than that in patients with other CYP3A5 genotypes (p < 0.05). In addition, the reduction in diastolic blood pressure (DBP) in patients with the CYP3A5*3*3 and CYP3A4*1G*1G genotypes was significantly higher than that in patients with other CYP3A5 and CYP3A4 genotypes, respectively (p < 0.05). Furthermore, we found that linkage disequilibrium exists between the CYP3A4 *1G and CYP3A5*3 alleles and observed that the most significant reduction in DBP occurred in patients with the *1/*1 and *3/*3 genotype. CONCLUSIONS: Our study demonstrates that amlodipine treatment may effectively control blood pressure (BP) for hypertensive patients following renal transplantation. Additionally, we found that the CYP3A5*3 polymorphism affects the antihypertensive efficacy of amlodipine in Chinese hypertensive patients after renal transplantation. .