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<i>CYP3A4</i> and <i>CYP3A5</i> Polymorphisms and Blood Pressure Response to Amlodipine among African-American Men and Women with Early Hypertensive Renal Disease

2009; Karger Publishers; Volume: 31; Issue: 2 Linguagem: Inglês

10.1159/000258688

1421-9670

Vibha Bhatnagar, Erin Garcia, Daniel T. O’Connor, Victoria H. Brophy, John E. Alcaraz, Erin Richard, George L. Bakris, John P. Middleton, Keith C. Norris, Jackson T. Wright, Leena Hiremath, Gabriel Contreras, Lawrence J. Appel, Michael S. Lipkowitz,

Hormonal Regulation and Hypertension

<i>Purpose:</i> To explore the association between <i>CYP3A4</i> and <i>CYP3A5</i> 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). <i>Methods:</i> Cox proportional hazards models were used to determine the risk of reaching a target mean arterial pressure (MAP) of ≤107 mm Hg by <i>CYP3A4</i> (A–392G and T16090C) and <i>CYP3A5</i> (A6986G) gene polymorphisms, stratified by MAP randomization group (low or usual) and controlling for other predictors for blood pressure response. <i>Results:</i> Women randomized to a usual MAP goal with an A allele at <i>CYP3A4</i> 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 <i>CYP3A4</i> 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 <i>CYP3A4 </i>T16090C SNP remained significant. C<i>YP3A5</i> A6986G was not associated with blood pressure response. <i>Conclusions:</i> Our findings suggest that blood pressure response to amlodipine among high-risk African-Americans appears to be determined by <i>CYP3A4</i> genotypes, and sex specificity may be an important consideration. Clinical applications of <i>CYP3A4</i> genotype testing for individualized treatment regimens warrant further study.