| A promoter polymorphism of the endothelial nitric oxide synthase gene is associated with reduced mRNA and protein expression in failing human myocardium. | |
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MedLine Citation:
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PMID: 20350698 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Alterations of endothelial nitric oxide synthase (eNOS) enzyme activity via eNOS gene polymorphisms have been associated with significant cardiovascular morbidity and mortality. Both the thymidine to cytosine transition mutation (T(-786)-->C) in the promoter region and the missense mutation in the exon 7 coding region of the eNOS gene (G(894)-->T) have been associated with several cardiovascular disease states. We hypothesized that heart transplant recipients who carried at least 1 allele of either of the polymorphisms would have reduced myocardial tissue expression of eNOS measured in the explanted heart. METHODS AND RESULTS: Genomic DNA was isolated from myocardial tissue samples obtained from 43 explanted human hearts using standard methods. Regions of the eNOS gene were amplified from genomic DNA with a polymerase chain reaction using specific primers. Protein expression of eNOS was measured by Western blot analysis. There was a statistically significant decrease in mean eNOS expression in samples containing at least one allele for the T(-786)-->C promoter polymorphism (P=.04) compared with patients homozygous for the T allele. There was no change in eNOS expression associated with the G(894)-->T exonic polymorphisms. CONCLUSIONS: Our data show in failing human myocardium that the T(-786)-->C promoter polymorphism is associated with reduced eNOS expression, whereas the G(894)-->T polymorphism of exon 7 is not associated with change in either eNOS mRNA or protein expression. Reduced eNOS expression associated with the promoter polymorphism may contribute to the vascular, contractile, and autonomic responses to ventricular failure. |
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Authors:
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Amit A Doshi; Mark T Ziolo; Honglan Wang; Emily Burke; Amanda Lesinski; Philip Binkley |
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Publication Detail:
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Type: Comparative Study; Journal Article Date: 2010-02-07 |
Journal Detail:
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Title: Journal of cardiac failure Volume: 16 ISSN: 1532-8414 ISO Abbreviation: J. Card. Fail. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-03-30 Completed Date: 2010-10-29 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 9442138 Medline TA: J Card Fail Country: United States |
Other Details:
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Languages: eng Pagination: 314-9 Citation Subset: IM |
Copyright Information:
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(c) 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH 43210, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Cytosine Nucleotides / genetics Down-Regulation / genetics Female Gene Expression Regulation Heart Failure / enzymology*, genetics*, pathology Humans Male Middle Aged Myocardium / enzymology*, pathology* Nitric Oxide Synthase Type III / antagonists & inhibitors, biosynthesis, genetics* Polymorphism, Single Nucleotide / genetics* Promoter Regions, Genetic / genetics* RNA, Messenger / antagonists & inhibitors, biosynthesis, genetics* Thymine Nucleotides / genetics |
| Grant Support | |
ID/Acronym/Agency:
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K24 EB002637-04/EB/NIBIB NIH HHS; K24 EB002637-05/EB/NIBIB NIH HHS; K24 HL004208-01/HL/NHLBI NIH HHS; K24 HL004208-02/HL/NHLBI NIH HHS; K24 HL004208-03/HL/NHLBI NIH HHS; R01 HL079283-01A1/HL/NHLBI NIH HHS; R01 HL079283-02/HL/NHLBI NIH HHS; R01 HL079283-03/HL/NHLBI NIH HHS; R01 HL079283-04/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytosine Nucleotides; 0/RNA, Messenger; 0/Thymine Nucleotides; EC 1.14.13.39/Nitric Oxide Synthase Type III |
| Comments/Corrections | |
Comment In:
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J Card Fail. 2010 Jul;16(7):618; author reply 618-9
[PMID:
20610239
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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