Document Detail

A single nucleotide polymorphism in the CYP4F2 but not CYP4A11 gene is associated with increased 20-HETE excretion and blood pressure.
MedLine Citation:
PMID:  18391101     Owner:  NLM     Status:  MEDLINE    
Arachidonic acid is a major fatty acid that can be metabolized by the cytochrome P450 enzyme to a number of bioactive eicosanoids. A major metabolite of this oxidation is 20-hydroxyeicosatetraenoic acid, which acts as a potent vasoconstrictor. However, in the kidney, its vasoconstrictor actions can be offset by its natriuretic properties. A guanine-to-adenine polymorphism in the CYP4F2 gene was associated with a reduction in 20-hydroxyeicosatetraenoic acid production in vitro. A thymidine-to-cytosine polymorphism in the CYP4A11 gene reduced catalytic activity by >50% in vitro and was associated with hypertension. The aim was to determine whether these 2 mutations are associated with urinary 20-hydroxyeicosatetraenoic acid excretion and blood pressure in humans. For the CYP4F2, 51% were homozygous for the G allele, 40% were carriers, and 9% were homozygous for the A allele. For CYP4A11, 72% were homozygous for the T allele, 25% were carriers, and 3% were homozygous for the C allele. The CYP4F2 GA/AA genotype was significantly associated with an increase in both 20-hydroxyeicosatetraenoic acid excretion and systolic blood pressure. The CYP4A11 CC/TC genotype was significantly associated with a reduction in 20-hydroxyeicosatetraenoic acid excretion but was not associated with blood pressure. We have demonstrated for the first time in humans that polymorphisms of the CYP4F2 and CYP4A11 genes have opposite effects on 20-hydroxyeicosatetraenoic acid excretion. The positive association between the CYP4F2 GA/AA genotype and both systolic blood pressure and 20-hydroxyeicosatetraenoic acid excretion strengthens a role for 20-hydroxyeicosatetraenoic acid in the modulation of blood pressure.
Natalie C Ward; I-Jung Tsai; Anne Barden; Frank M van Bockxmeer; Ian B Puddey; Jonathan M Hodgson; Kevin D Croft
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-04-07
Journal Detail:
Title:  Hypertension     Volume:  51     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-04-18     Completed Date:  2008-05-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1393-8     Citation Subset:  IM    
Schools of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
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MeSH Terms
Blood Pressure / genetics*,  physiology
Cytochrome P-450 Enzyme System / genetics*
Hydroxyeicosatetraenoic Acids / urine*
Hypertension / genetics,  physiopathology,  urine
Middle Aged
Mutation / genetics
Polymorphism, Single Nucleotide / genetics*
Regression Analysis
Reg. No./Substance:
0/Hydroxyeicosatetraenoic Acids; 79551-86-3/20-hydroxy-5,8,11,14-eicosatetraenoic acid; 9035-51-2/Cytochrome P-450 Enzyme System; EC protein, human; EC protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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