Published Online
on December 13, 2004

A more recent version of this article appeared on February 1, 2005

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Submitted on July 9, 2004
Revised on July 28, 2004

Association Between the CYP3A5 Genotype and Blood Pressure

Herbert Ho^*; Amar Pinto; Stephen D. Hall; David A. Flockhart; Lang Li; Todd C. Skaar; Peter Cadman; Daniel T. O’Connor; Urban Wagner; Naomi S. Fineberg; and Myron H. Weinberger

From the Divisions of Clinical Pharmacology (H.H., A.P., S.D.H., D.A.F., T.C.S.), Biostatistics (L.L., N.S.F.), and Endocrinology and Metabolism (U.W., M.H.W.), Department of Medicine, Indiana University School of Medicine, Indianapolis; and Division of Nephrology (P.C., D.T.O.), Department of Medicine, University of California San Diego School of Medicine.

^* To whom correspondence should be addressed. E-mail: heho{at}iupui.edu.

Abstract--We tested the hypothesis that the presence of a CYP3A5*1 allele is associated with increases in blood pressure in 2 studies of subjects with a total of 683 participants. The first study involving 271 subjects was part of a longitudinal study conducted at Indiana University Medical Center that consisted of 2 phases. The first phase studied the relationship of salt sensitivity with blood pressure, whereas the second phase, conducted 26 years later, studied the relationship between blood pressure, carbohydrate intolerance, and vascular compliance in the same subjects. The second study was a cross-sectional evaluation of 412 normotensive and hypertensive subjects conducted at the University of California San Diego. The second study (Mantel-Haenszel ² test; P=0.05) showed that a greater proportion of black participants with poor blood pressure control had CYP3A5*1/*1 genotype. Evaluation of the untreated blood pressure from phase 1 of the first study showed that the blacks with CYP3A5*3/*3 (146±35 mm Hg) had a higher systolic blood pressure than those with the *1/*3 (119±14.1 mm Hg; P=0.0006) and *1/*1 (125±17.4 mm Hg; P=0.009) genotypes. For blacks in study 2, the CYP3A5*1 allele was more common in hypertensives (Fisher exact test; P=0.025) than normotensives. In whites there was no association between CYP3A5 genotype and blood pressure in either study. We conclude that although untreated blood pressure may be higher in blacks with the CYP3A5*3/*3 genotype, the CYP3A5*1 allele may be associated with hypertension that is more refractory to treatment in this ethnic group.

Key words: cytochrome p450 • blood pressure • genetics • polymorphism

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