Document Detail


Association of variants in NEDD4L with blood pressure response and adverse cardiovascular outcomes in hypertensive patients treated with thiazide diuretics.
MedLine Citation:
PMID:  23353631     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Single-nucleotide polymorphisms (SNPs) in NEDD4L may influence the ability of the NEDD4L protein to reduce epithelial sodium channel expression. A variant in NEDD4L, rs4149601, was associated with antihypertensive response and cardiovascular outcomes during treatment with thiazide diuretics and β-blockers in a Swedish population. We sought to further evaluate associations between NEDD4L polymorphisms, blood pressure response and cardiovascular outcomes with thiazide diuretics and β-blockers.
METHODS: Four SNPs, rs4149601, rs292449, rs1008899 and rs75982813, were genotyped in 767 patients from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) clinical trial and association was assessed with blood pressure response to hydrochlorothiazide and atenolol. One SNP, rs4149601, was also genotyped in 1345 patients from the International Verapmil SR Trandolapril Study (INVEST), and association was examined with adverse cardiovascular outcomes relative to hydrochlorothiazide treatment.
RESULTS: Significant associations or trends were found between rs4149601, rs292449, rs75982813 and rs1008899 and decreases in blood pressure in whites on hydrochlorothiazide, and a significant association was observed with increasing copies of the GC rs4149601-rs292449 haplotype and greater blood pressure response to hydrochlorothiazide in whites (P = 0.0006 and 0.006, SBP and DBP, respectively). Significant associations were also seen with rs4149601 and an increased risk for adverse cardiovascular outcomes in whites not treated with hydrochlorothiazide [P = 0.022, odds ratio (95% confidence interval) = 10.65 (1.18-96.25)].
CONCLUSION: NEDD4L rs4149601, rs292449 and rs75982813 may be predictors for blood pressure response to hydrochlorothiazide in whites, and NEDD4L rs4149601 may be a predictor for adverse cardiovascular outcomes in whites not treated with hydrochlorothiazide.
Authors:
Caitrin W McDonough; Sarah E Burbage; Julio D Duarte; Yan Gong; Taimour Y Langaee; Stephen T Turner; John G Gums; Arlene B Chapman; Kent R Bailey; Amber L Beitelshees; Eric Boerwinkle; Carl J Pepine; Rhonda M Cooper-DeHoff; Julie A Johnson
Publication Detail:
Type:  Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hypertension     Volume:  31     ISSN:  1473-5598     ISO Abbreviation:  J. Hypertens.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-07     Completed Date:  2013-08-29     Revised Date:  2014-04-02    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  698-704     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adult
Blood Pressure / genetics*
Endosomal Sorting Complexes Required for Transport / genetics*
Female
Humans
Hypertension / drug therapy*,  physiopathology
Male
Middle Aged
Polymorphism, Single Nucleotide
Prospective Studies
Sodium Chloride Symporter Inhibitors / therapeutic use*
Treatment Outcome
Ubiquitin-Protein Ligases / genetics*
Grant Support
ID/Acronym/Agency:
K23HL091120/HL/NHLBI NIH HHS; T32 DK007518/DK/NIDDK NIH HHS; U01 GM074492/GM/NIGMS NIH HHS; U01-GM074492/GM/NIGMS NIH HHS; UL1 TR000064/TR/NCATS NIH HHS; UL1 TR000064/TR/NCATS NIH HHS; UL1 TR000135/TR/NCATS NIH HHS; UL1 TR000454/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
0/Endosomal Sorting Complexes Required for Transport; 0/Sodium Chloride Symporter Inhibitors; EC 6.3.2.19/Nedd4 ubiquitin protein ligases; EC 6.3.2.19/Ubiquitin-Protein Ligases
Comments/Corrections

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


Previous Document:  Nanostructured high-strength molybdenum alloys with unprecedented tensile ductility.
Next Document:  Take the (RN)A-train: Localization of mRNA to the endoplasmic reticulum.