| Pharmacogenetic Association of NOS3 Variants with Cardiovascular Disease in Patients with Hypertension: The GenHAT Study. | |
| | |
MedLine Citation:
|
PMID: 22470539 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
Nitric oxide synthase 3 (NOS3) catalyzes production of NO in the endothelium and may play a role in cardiovascular disease (CVD). We assessed the pharmacogenetic associations of three NOS3 polymorphisms and three antihypertensive drugs with CVD outcomes. Hypertensive subjects (n = 30,280) from a multi-center, double-blind clinical trial were randomized to chlorthalidone, amlodipine, or lisinopril treatment (mean follow up, 4.9 years). Outcomes included coronary heart disease (CHD: fatal CHD and nonfatal myocardial infarction); stroke; heart failure (fatal, requiring hospitalization, or outpatient treatment); all-cause mortality; and end-stage renal disease (ESRD). Main effects of NOS3 variants on outcome and genotype-treatment interactions were tested. For NOS3 -690 C>T (rs3918226), a higher hazard ratio (HR) was found in minor allele carriers for CHD (CC = 1.00, CT+TT = 1.12 (95% confidence interval (CI) = 1.00-1.26), P = 0.048). For NOS3 -922 A>G (rs1800779), a higher HR was found in minor allele carriers for heart failure (AA = 1.00, AG+GG = 1.10 (CI = 1.00-1.21), P = 0.046). Significant pharmacogenetic findings were observed for stroke and all-cause mortality. For -690 C>T, a lower HR was observed for stroke in minor allele carriers when treated with amlodipine versus lisinopril (CC = 0.85 (CI = 0.73-0.99), CT+TT = 0.49 (CI = 0.31-0.80), P = 0.04). For glu298asp G>T (rs1799983), a lower HR was observed for all-cause mortality in minor allele carriers when treated with amlodipine versus lisinopril (GG = 1.01 (CI = 0.91-1.13), GT+TT = 0.85 (CI = 0.75-0.97), P = 0.04). We observed significant associations with NOS3 variants and CHD and heart failure and significant pharmacogenetic effects for stroke and all cause mortality. This suggests that NOS3 variants may potentially provide useful clinical information with respect to treatment decisions in the future. |
| | |
Authors:
|
Xue Zhang; Amy I Lynch; Barry R Davis; Charles E Ford; Eric Boerwinkle; John H Eckfeldt; Catherine Leiendecker-Foster; Donna K Arnett |
Related Documents
:
|
17719319 - Predictors of in-stent restenosis and patient outcome after percutaneous coronary inter... 12537839 - Prevalence of arterial hypertension and myocardial infarction in relation to subjective... 2502249 - First myocardial infarctions in asian and white men. 23569569 - Coronary spasm after the topical use of cocaine in nasal surgery. 18813179 - Admission glycemia and markers of inflammation are independent outcome predictors in pr... 12668699 - Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunct... 22742529 - Myocardial infarction with normal coronary arteries is common and associated with norma... 9509249 - The open-artery hypothesis. 10451239 - Clinical application of markers of cardiac injury: basic concepts and new considerations. |
Publication Detail:
|
Type: Journal Article Date: 2012-03-28 |
Journal Detail:
|
Title: PloS one Volume: 7 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2012 |
Date Detail:
|
Created Date: 2012-04-03 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States |
Other Details:
|
Languages: eng Pagination: e34217 Citation Subset: IM |
Affiliation:
|
Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Harvesting Electricity with Geobacter bremensis Isolated from Compost.
Next Document: No Evidence for Infection of UK Prostate Cancer Patients with XMRV, BK Virus, Trichomonas vaginalis ...