CYP3A4 and CYP3A5 polymorphisms and blood pressure response to amlodipine among African-American men and women with early hypertensive renal disease.
PURPOSE: 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, V; Garcia, EP; O'Connor, DT; Brophy, VH; Alcaraz, J; Richard, E; Bakris, GL; Middleton, JP; Norris, KC; Wright, J; Hiremath, L; Contreras, G; Appel, LJ; Lipkowitz, MS; AASK Study Investigators,
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