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Am J Nephrol. 2010;31(2):95-103. doi: 10.1159/000258688. Epub 2009 Nov 12.

CYP3A4 and CYP3A5 polymorphisms and blood pressure response to amlodipine among African-American men and women with early hypertensive renal disease.

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  • 1University of California-San Diego, 3350 La Jolla Village Drive, San Diego, CA 92131, USA. vbhatnag@ucsd.edu

Abstract

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.

PMID:
19907160
PMCID:
PMC2853591
DOI:
10.1159/000258688
[PubMed - indexed for MEDLINE]
Free PMC Article
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