HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 95/3/1297    most recent 00322.2003v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (45) Citing Articles via Google Scholar Google Scholar Articles by Givens, R. C. Articles by Watkins, P. B. Search for Related Content PubMed PubMed Citation Articles by Givens, R. C. Articles by Watkins, P. B.

CYP3A5 genotype predicts renal CYP3A activity and blood pressure in healthy adults

¹General Clinical Research Center, University of North Carolina School of Medicine, Chapel Hill 27514; ²Duke University School of Medicine, Durham, North Carolina 27705; ³Department of Pharmaceutics, University of Washington, Seattle, Washington 98195; and ⁴Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee 38105

Submitted 31 March 2003 ; accepted in final form 15 May 2003

ABSTRACT

A single-nucleotide polymorphism (A6986G) in the cytochrome P-450 3A5 (CYP3A5) gene distinguishes an expressor (*1) and a reduced-expressor (*3) allele and largely predicts CYP3A5 content in liver and intestine. CYP3A5 is the prevailing CYP3A isoform in kidney. We report that, among renal microsomes from 21 organ donors, those from *1/*3 individuals had at least eightfold higher mean kidney microsomal CYP3A5 content and 18-fold higher mean CYP3A catalytic activity than did those from *3/*3 individuals (P = 0.0001 and P = 0.0137, respectively). We also report significant associations between the A6986G polymorphism and systolic blood pressure (P = 0.0007), mean arterial pressure (P = 0.0075), and creatinine clearance (P = 0.0035) among 25 healthy African-American adults. These associations remained significant when sex, age, and body mass index were taken into account. The mean systolic blood pressure of homozygous CYP3A5 expressors (*1/*1) exceeded that of homozygous nonexpressors (*3/*3) by 19.3 mmHg. We speculate whether a high CYP3A5 expressor allele frequency among African-Americans may contribute to a high prevalence of sodium-sensitive hypertension in this population.

cytochrome P-450 3A5; single-nucleotide polymorphism; kidney; sodium sensitivity

This article has been cited by other articles:

				D. A. Calhoun, D. Jones, S. Textor, D. C. Goff, T. P. Murphy, R. D. Toto, A. White, W. C. Cushman, W. White, D. Sica, et al. Resistant Hypertension: Diagnosis, Evaluation, and Treatment: A Scientific Statement From the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research Circulation, June 24, 2008; 117(25): e510 - e526. [Abstract] [Full Text] [PDF]

				D. A. Calhoun, D. Jones, S. Textor, D. C. Goff, T. P. Murphy, R. D. Toto, A. White, W. C. Cushman, W. White, D. Sica, et al. Resistant Hypertension: Diagnosis, Evaluation, and Treatment: A Scientific Statement From the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research Hypertension, June 1, 2008; 51(6): 1403 - 1419. [Abstract] [Full Text] [PDF]

				K. Kosuge, A. I. Chuang, S. Uematsu, K. P. Tan, K. Ohashi, B. C.B. Ko, and S. Ito Discovery of Osmosensitive Transcriptional Regulation of Human Cytochrome P450 3As by the Tonicity-Responsive Enhancer Binding Protein (Nuclear Factor of Activated T Cells 5) Mol. Pharmacol., October 1, 2007; 72(4): 826 - 837. [Abstract] [Full Text] [PDF]

				M. Yazdanpanah, Y. S. Aulchenko, A. Hofman, J. A.M.J.L. Janssen, F. A. Sayed-Tabatabaei, R. H.N. van Schaik, O. H. Klungel, B. H.C.H. Stricker, H. A.P. Pols, J. C.M. Witteman, et al. Effects of the Renin-Angiotensin System Genes and Salt Sensitivity Genes on Blood Pressure and Atherosclerosis in the Total Population and Patients With Type 2 Diabetes Diabetes, July 1, 2007; 56(7): 1905 - 1912. [Abstract] [Full Text] [PDF]

				Amal Al Omari and D. J. Murry Pharmacogenetics of the Cytochrome P450 Enzyme System: Review of Current Knowledge and Clinical Significance Journal of Pharmacy Practice, June 1, 2007; 20(3): 206 - 218. [Abstract] [PDF]

				C. B. Eap, M. Bochud, R. C. Elston, P. Bovet, M. P. Maillard, J. Nussberger, L. Schild, C. Shamlaye, and M. Burnier CYP3A5 and ABCB1 Genes Influence Blood Pressure and Response to Treatment, and Their Effect Is Modified by Salt Hypertension, May 1, 2007; 49(5): 1007 - 1014. [Abstract] [Full Text] [PDF]

				Y. Dai, M. F. Hebert, N. Isoherranen, C. L. Davis, C. Marsh, D. D. Shen, and K. E. Thummel EFFECT OF CYP3A5 POLYMORPHISM ON TACROLIMUS METABOLIC CLEARANCE IN VITRO Drug Metab. Dispos., May 1, 2006; 34(5): 836 - 847. [Abstract] [Full Text] [PDF]

				C. Xing, B. E.K. Klein, R. Klein, G. Jun, K. E. Lee, and S. K. Iyengar Genome-Wide Linkage Study of Retinal Vessel Diameters in the Beaver Dam Eye Study Hypertension, April 1, 2006; 47(4): 797 - 802. [Abstract] [Full Text] [PDF]

				J. S. McCune, L. J. Risler, B. R. Phillips, K. E. Thummel, D. Blough, and D. D. Shen CONTRIBUTION OF CYP3A5 TO HEPATIC AND RENAL IFOSFAMIDE N-DECHLOROETHYLATION Drug Metab. Dispos., July 1, 2005; 33(7): 1074 - 1081. [Abstract] [Full Text] [PDF]

				H. Ho, A. Pinto, S. D. Hall, D. A. Flockhart, L. Li, T. C. Skaar, P. Cadman, D. T. O'Connor, U. Wagner, N. S. Fineberg, et al. Association Between the CYP3A5 Genotype and Blood Pressure Hypertension, February 1, 2005; 45(2): 294 - 298. [Abstract] [Full Text] [PDF]

				W. Huang, Y. S. Lin, D. J. McConn II, J. C. Calamia, R. A. Totah, N. Isoherranen, M. Glodowski, and K. E. Thummel EVIDENCE OF SIGNIFICANT CONTRIBUTION FROM CYP3A5 TO HEPATIC DRUG METABOLISM Drug Metab. Dispos., December 1, 2004; 32(12): 1434 - 1445. [Abstract] [Full Text] [PDF]