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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Association of CYP3A5 genotypes with blood pressure and renal function in African families
Journal of Hypertension, Volume 24, No. 5, Year 2006
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Description
Objective: Renal cytochrome P450 3A5 (CYP3A5) activity has been associated with blood pressure and salt sensitivity in humans. We determined whether CYP3A5 polymorphisms are associated with ambulatory blood pressure (ABP) and with glomerular filtration rate (GFR) in African families. Methods: Using a cross-sectional design, 375 individuals from 72 families, each with at least two hypertensive siblings, were recruited through a hypertension register in the Seychelles (Indian Ocean). We analyzed the association between the CYP3A5 alleles (*1, *3, *6 and *7) and ABP, GFR and renal sodium handling (fractional excretion of lithium), from pedigree data, allowing for other covariates and familial correlations. Results: CYP3A5*1 carriers increased their daytime systolic and diastolic ABP with age (0.55 and 0.23 mmHg/ year) more than non-carriers (0.21 and 0.04 mmHg/year). CYP3A5*1 had a significant main effect on daytime systolic/diastolic ABP [regression coefficient (SE): -29.6 (10.0)/-8.2 (4.1) mmHg, P = 0.003/0.045, respectively] and this effect was modified by age (CYP3A5*1 X age interactions, P = 0.017/0.018). For night-time ABP, the effect of CYP3A5*1 was modified by urinary sodium excretion, not by age. For renal function, CYP3A5*1 carriers had a 7.6(3.8) ml/min lower GFR (P = 0.045) than non-carriers. Proximal sodium reabsorption decreased with age in non-carriers, but not in CYP3A5*1 carriers (P for interaction = 0.02). Conclusions: These data demonstrate that CYP3A5 polymorphisms are associated with ambulatory BP, CYP3A5*1 carriers showing a higher age- and sodium-related increase in ABP than non-carriers. The age effect may be due, in part, to the action of CYP3A5 on renal sodium handling. © 2006 Lippincott Williams & Wilkins.
Authors & Co-Authors
Bochud, Murielle
United States, Cleveland
Case Western Reserve University
Switzerland, Lausanne
Institut Universitaire de Médecine Sociale et Préventive Lausanne
Eap, Chin B.
Unknown Affiliation
Elston, Robert C.
United States, Cleveland
Case Western Reserve University
Bovet, Pascal
Switzerland, Lausanne
Institut Universitaire de Médecine Sociale et Préventive Lausanne
Switzerland, Bern
Ministry of Health
Maillard, Marc P.
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Schild, Laurent
Switzerland, Lausanne
Université de Lausanne Unil
Shamlaye, Conrad F.
Switzerland, Bern
Ministry of Health
Burnier, Michel
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Statistics
Citations: 47
Authors: 8
Affiliations: 5
Identifiers
Doi:
10.1097/01.hjh.0000222763.84605.4a
ISSN:
02636352
Research Areas
Noncommunicable Diseases
Study Design
Cross Sectional Study
Study Locations
Seychelles