CYP3A5 and ABCB1 genes influence blood pressure and response to treatment, and their effect is modified by salt.

Details

Serval ID
serval:BIB_271777C1AEDD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
CYP3A5 and ABCB1 genes influence blood pressure and response to treatment, and their effect is modified by salt.
Journal
Hypertension
Author(s)
Eap C.B., Bochud M., Elston R.C., Bovet P., Maillard M.P., Nussberger J., Schild L., Shamlaye C., Burnier M.
ISSN
1524-4563[electronic]
Publication state
Published
Issued date
2007
Peer-reviewed
Oui
Volume
49
Number
5
Pages
1007-14
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
The permeability-glycoprotein efflux-transporter encoded by the multidrug resistance 1 (ABCB1) gene and the cytochromes P450 3A4/5 encoded by the CYP3A4/5 genes are known to interact in the transport and metabolism of many drugs. Recent data have shown that the CYP3A5 genotypes influence blood pressure and that permeability-glycoprotein activity might influence the activity of the renin-angiotensin system. Hence, these 2 genes may contribute to blood pressure regulation in humans. We analyzed the association of variants of the ABCB1 and CYP3A5 genes with ambulatory blood pressure, plasma renin activity, plasma aldosterone, endogenous lithium clearance, and blood pressure response to treatment in 72 families (373 individuals; 55% women; mean age: 46 years) of East African descent. The ABCB1 and CYP3A5 genes interact with urinary sodium excretion in their effect on ambulatory blood pressure (daytime systolic: P=0.05; nighttime systolic and diastolic: P<0.01), suggesting a gene-gene-environment interaction. The combined action of these genes is also associated with postproximal tubular sodium reabsorption, plasma renin activity, plasma aldosterone, and with an altered blood pressure response to the angiotensin-converting enzyme inhibitor lisinopril (P<0.05). This is the first reported association of the ABCB1 gene with blood pressure in humans and demonstration that genes encoding for proteins metabolizing and transporting drugs and endogenous substrates contribute to blood pressure regulation.
Keywords
Absorption, Adult, Aldosterone, Angiotensin-Converting Enzyme Inhibitors, Blood Pressure, Blood Pressure Monitoring, Ambulatory, Cytochrome P-450 CYP3A, Cytochrome P-450 Enzyme System, Female, Humans, Hypertension, Kidney Tubules, Proximal, Lisinopril, Lithium, Male, Middle Aged, Natriuresis, Organic Anion Transporters, P-Glycoprotein, Renin, Sodium Chloride
Pubmed
Web of science
Create date
05/02/2008 13:38
Last modification date
20/08/2019 13:05
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