title: CYP3A4*1G and CYP3A5*3 genetic polymorphisms alter the antihypertensive efficacy of amlodipine in patients with hypertension following renal transplantation .
abstract: OBJECTIVE
  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.Materials: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. .
authors.forename: Yun
authors.initials: Y
authors.lastname: Huang
authors.forename: Gaiyan
authors.initials: G
authors.lastname: Wen
authors.forename: Yao
authors.initials: Y
authors.lastname: Lu
authors.forename: Jia
authors.initials: J
authors.lastname: Wen
authors.forename: Ying
authors.initials: Y
authors.lastname: Ji
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Xing
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Juan
authors.initials: J
authors.lastname: Wen
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000328:Adult; D017311:Amlodipine / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002681:China; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D016896:Treatment Outcome
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D017311:Amlodipine; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human