CYP3A4 and CYP3A5 polymorphisms and blood pressure response to amlodipine among African-American men and women with early hypertensive renal disease.
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.
Bhatnagar
Vibha
V
University of California-San Diego, 3350 La Jolla Village Drive, San Diego, CA 92131, USA. vbhatnag@ucsd.edu
Garcia
Erin P
EP
O'Connor
Daniel T
DT
Brophy
Victoria H
VH
Alcaraz
John
J
Richard
Erin
E
Bakris
George L
GL
Middleton
John P
JP
Norris
Keith C
KC
Wright
Jackson
J
Hiremath
Leena
L
Contreras
Gabriel
G
Appel
Lawrence J
LJ
Lipkowitz
Michael S
MS
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
D017311:Amlodipine; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human