Document Detail


CYP4A11 T8590C polymorphism, salt-sensitive hypertension, and renal blood flow.
MedLine Citation:
PMID:  21873888     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE AND METHODS: A loss-of-function cytosine (C) for thymidine (T) transition at nucleotide 8590 of CYP4A11 has been associated with increased blood pressure in humans. We tested the hypothesis that CYP4A11 T8590C genotype is associated with salt sensitivity in the International Hypertensive Pathotype cohort.
RESULTS: CYP4A11 T8590C genotype was associated with hypertension in whites. Among normotensive individuals, CYP4A11 T8590C genotype was associated with mean arterial pressure (MAP) during both high and low salt diets, such that there was no relationship between genotype and salt sensitivity of blood pressure. Among hypertensive individuals, CYP4A11 T8590C genotype did not associate with MAP during high salt intake, whereas MAP decreased with increasing number of C alleles during salt restriction. Consequently, among hypertensive individuals, change in MAP with salt restriction was greatest in individuals homozygous for the C allele (-10.9 ± 9.9, -11.1 ± 12.3, and -18.8 ± 12.0 mmHg in TT, CT, and CC groups, respectively, P = 0.02). In both normotensive and hypertensive individuals, individuals homozygous for the C allele exhibited an attenuated increase in renal blood flow during high salt. CYP4A11 genotype did not affect pressor responses to Angiotensin II in normotensive or hypertensive individuals.
CONCLUSION: The loss-of-function CYP4A11 8590C allele is associated with a diagnosis of hypertension and, in normotensive individuals, with higher blood pressure regardless of salt intake. Among hypertensive individuals, the C allele is associated with salt-sensitive blood pressure. Impaired renal vasodilation during high salt intake may contribute to salt sensitivity. Studies are needed to determine whether CYP4A11 T8590C genotype predicts responses to medications that affect sodium homeostasis in hypertensive individuals.
Authors:
Jonathan S Williams; Paul N Hopkins; Xavier Jeunemaitre; Nancy J Brown
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of hypertension     Volume:  29     ISSN:  1473-5598     ISO Abbreviation:  J. Hypertens.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-13     Completed Date:  2012-01-16     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  1913-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Alleles
Angiotensin II / pharmacology
Blood Pressure / drug effects,  genetics,  physiology
Cytochrome P-450 Enzyme System / genetics*
Diet, Sodium-Restricted
Female
Genetic Association Studies
Humans
Hypertension / diet therapy,  etiology,  genetics*,  physiopathology
Male
Middle Aged
Norepinephrine / pharmacology
Polymorphism, Single Nucleotide
Renal Circulation / genetics*,  physiology
Sodium Chloride, Dietary / administration & dosage
Grant Support
ID/Acronym/Agency:
DK038226/DK/NIDDK NIH HHS; HL055000/HL/NHLBI NIH HHS; HL060906/HL/NHLBI NIH HHS; HL084236/HL/NHLBI NIH HHS; LM008748/LM/NLM NIH HHS; P01 DK038226/DK/NIDDK NIH HHS; P01 DK038226-26/DK/NIDDK NIH HHS; RR002635/RR/NCRR NIH HHS; RR024975/RR/NCRR NIH HHS; RR025758/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Sodium Chloride, Dietary; 11128-99-7/Angiotensin II; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.15.3/CYP4A11 protein, human; X4W3ENH1CV/Norepinephrine
Comments/Corrections

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


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