title: CYP3A4 and CYP3A5 polymorphisms and blood pressure response to amlodipine among African-American men and women with early hypertensive renal disease.
abstract: OBJECTIVE
  To explore the association between CYP3A4 and CYP3A5 gene polymorphisms and blood pressure response to amlodipine among participants from the African-American Study of Kidney Disease and Hypertension Trial randomized to amlodipine (n = 164).
  
  
  METHODS
  Cox proportional hazards models were used to determine the risk of reaching a target mean arterial pressure (MAP) of < or =107 mm Hg by CYP3A4 (A-392G and T16090C) and CYP3A5 (A6986G) gene polymorphisms, stratified by MAP randomization group (low or usual) and controlling for other predictors for blood pressure response.
  
  
  RESULTS
  Women randomized to a usual MAP goal with an A allele at CYP3A4 A-392G were more likely to reach a target MAP of 107 mm Hg. The adjusted hazard ratio (AA/AG compared to GG) with 95% confidence interval was 3.41 (1.20-9.64; p = 0.020). Among participants randomized to a lower MAP goal, those with the C allele at CYP3A4 T16090C were more likely to reach target MAP: The adjusted hazard ratio was 2.04 (1.17-3.56; p = 0.010). After adjustment for multiple testing using a threshold significance level of p = 0.016, only the CYP3A4 T16090C SNP remained significant. CYP3A5 A6986G was not associated with blood pressure response.
  
  
  CONCLUSIONS
  Our findings suggest that blood pressure response to amlodipine among high-risk African-Americans appears to be determined by CYP3A4 genotypes, and sex specificity may be an important consideration. Clinical applications of CYP3A4 genotype testing for individualized treatment regimens warrant further study.
authors.affiliation: University of California-San Diego, 3350 La Jolla Village Drive, San Diego, CA 92131, USA. vbhatnag@ucsd.edu
authors.forename: Vibha
authors.initials: V
authors.lastname: Bhatnagar
authors.forename: Erin P
authors.initials: EP
authors.lastname: Garcia
authors.forename: Daniel T
authors.initials: DT
authors.lastname: O'Connor
authors.forename: Victoria H
authors.initials: VH
authors.lastname: Brophy
authors.forename: John
authors.initials: J
authors.lastname: Alcaraz
authors.forename: Erin
authors.initials: E
authors.lastname: Richard
authors.forename: George L
authors.initials: GL
authors.lastname: Bakris
authors.forename: John P
authors.initials: JP
authors.lastname: Middleton
authors.forename: Keith C
authors.initials: KC
authors.lastname: Norris
authors.forename: Jackson
authors.initials: J
authors.lastname: Wright
authors.forename: Leena
authors.initials: L
authors.lastname: Hiremath
authors.forename: Gabriel
authors.initials: G
authors.lastname: Contreras
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Appel
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lipkowitz
mesh_terms: D001741:Black or African American; D000368:Aged; D000483:Alleles; D017311:Amlodipine / Q000494:pharmacology*; D001794:Blood Pressure; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D017311:Amlodipine; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human