CYP3A41G and CYP3A53 genetic polymorphisms alter the antihypertensive efficacy of amlodipine in patients with hypertension following renal transplantation

• Published in: International journal of clinical pharmacology and therapeutics Vol. 55; no. 2; pp. 109 - 118
• Main Authors: Huang, Yun, Wen, Gaiyan, Lu, Yao, Wen, Jia, Ji, Ying, Xing, Xiaowei, Li, Ying, Wen, Juan, Yuan, Hong
• Format: Journal Article
• Language: English
• Published: Germany Dustri - Verlag Dr. Karl Feistle GmbH & Co. KG 01.02.2017
• Subjects: Adult; Amlodipine - therapeutic use; Antihypertensive Agents - therapeutic use; ATP Binding Cassette Transporter, Subfamily B - genetics; ATP Binding Cassette Transporter, Subfamily B - metabolism; Blood pressure; Blood Pressure - drug effects; Calcium Channel Blockers - therapeutic use; China; Cytochrome P-450 CYP3A - genetics; Cytochrome P-450 CYP3A - metabolism; Diuretics; Female; Gene Frequency; Genotype; Genotype & phenotype; Humans; Hypertension; Hypertension - diagnosis; Hypertension - drug therapy; Hypertension - etiology; Hypertension - physiopathology; Kidney Transplantation - adverse effects; Linkage Disequilibrium; Male; Middle Aged; Pharmacogenetics; Pharmacogenomic Variants; Phenotype; Treatment Outcome
• ISSN: 0946-1965
• DOI: 10.5414/CP202559

Previous studies have determined that CYP3A and multidrug resistance protein 1 (MDR1) polymorphisms can affect the pharmacokinetics and pharmacodynamics of amlodipine in both healthy subjects and those with early hypertensive renal disease. In the current study, our objective was to analyze the association between the CYP3A4*1G, CYP3A5*3, and MDR1 C3435T gene polymorphisms and the antihypertensive efficacy of amlodipine in hypertensive patients after renal transplantation. Blood samples were collected from 76 patients on amlodipine therapy (5 mg/d). 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. 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. 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.
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