| CYP2C9 genotype modifies activity of the renin-angiotensin-aldosterone system in hypertensive men. | |
| | |
MedLine Citation:
|
PMID: 19593208 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: Two variants of the CYP2C9 gene, CYP2C9*2 and CYP2C9*3, have been indicated to have impaired enzyme function, and thus suspected to reduce the formation of the active metabolite of losartan. Cytochrome P450 (CYP) enzymes are also involved in eicosanoid biosynthesis and regulation of blood pressure (BP) and sodium homeostasis. METHODS: We studied the impact of these variants on BP response to losartan and three other antihypertensive drugs and on baseline indicators of the activity of the renin-angiotensin-aldosterone system. The participants were 217 moderately hypertensive Finnish men that participated in the double-blind, cross-over, placebo-controlled GENRES Study. RESULTS: BP responses to losartan did not differ between CYP2C9*2 or CYP2C9*3 allele carriers and CYP2C9*1*1 patients. A suggestive finding of less pronounced ambulatory BP response to losartan in CYP2C9*1*3 patients with low-normal kidney function was made. At baseline of the GENRES Study, CYP2C9*1*3 patients had significantly lower plasma renin activity and aldosterone levels than CYP2C9*1*1 patients (both P values 0.004). In a replication study in patients with treatment-resistant hypertension, men with CYP2C9*3 allele also had lower plasma renin activity (P = 0.03) and aldosterone levels (P = 0.18). In addition, these men had attenuated renin and aldosterone responses in captopril challenge test (P = 0.29 and 0.006, respectively). CONCLUSION: The CYP2C9*3 allele was associated with lower activity of the renin-angiotensin-aldosterone system in hypertensive men, which may reflect a more efficient sodium reabsorption capacity. CYP2C9*2 and CYP2C9*3 alleles do not influence the antihypertensive effect of losartan in men with essential hypertension and normal kidney function. |
| | |
Authors:
|
Kati M Donner; Timo P Hiltunen; Timo Suonsyrj??; Tuula Hannila-Handelberg; Ilkka Tikkanen; Miia Antikainen; Ari Hirvonen; Kimmo Kontula |
Related Documents
:
|
17215648 - Resistant hypertension: prevalence and evolving concepts. 8390508 - Chronic inhibition of endopeptidase 24.11 in essential hypertension: evidence for enhan... 9683048 - Genetic determination of plasma aldosterone levels in essential hypertension. 12172288 - Vasoactive modulators during and after craniotomy: relation to postoperative hypertension. 1623758 - Effects of peep on respiratory mechanics after open heart surgery. 20111858 - Central venous pressure measurements improve the accuracy of leg raising-induced change... |
Publication Detail:
|
Type: Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Journal of hypertension Volume: 27 ISSN: 1473-5598 ISO Abbreviation: J. Hypertens. Publication Date: 2009 Oct |
Date Detail:
|
Created Date: 2009-11-09 Completed Date: 2010-01-28 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8306882 Medline TA: J Hypertens Country: England |
Other Details:
|
Languages: eng Pagination: 2001-9 Citation Subset: IM |
Affiliation:
|
Department of Medicine, University of Helsinki, FIN-00029 Helsinki, Finland. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adult Aldosterone / blood Amlodipine / therapeutic use Antihypertensive Agents / therapeutic use* Aryl Hydrocarbon Hydroxylases / genetics* Bisoprolol / therapeutic use Cross-Over Studies Double-Blind Method Drug Resistance / genetics Electrolytes / blood Gene Frequency Genotype Humans Hypertension, Renal / drug therapy*, genetics* Losartan / therapeutic use* Male Middle Aged Placebos Renin / blood Renin-Angiotensin System / drug effects, genetics |
| Chemical | |
Reg. No./Substance:
|
0/Antihypertensive Agents; 0/Electrolytes; 0/Placebos; 114798-26-4/Losartan; 52-39-1/Aldosterone; 66722-44-9/Bisoprolol; 88150-42-9/Amlodipine; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/CYP2C9 protein, human; EC 3.4.23.15/Renin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Congenital glaucoma: CYP1B1 mutations in Israeli Bedouin kindreds.
Next Document: Calcium-sensing receptors modulate renin release in vivo and in vitro in the rat.