Abstract:
OBJECTIVES:This study sought to investigate the impact of a common T(-786)C single-nucleotide polymorphism (SNP) in the promoter of the endothelial nitric oxide synthase (eNOS, NOS3) gene on cardiovascular (CV) death in a prospective cohort study. BACKGROUND:The T(-786)C SNP eNOS gene implies a blunted endothelium-dependent vasodilation in hypertensive patients and was associated with multivessel coronary artery disease in cross-sectional studies, but it remained unsettled whether it carried prognostic information. METHODS:In consecutive white patients of the GENICA (Genetic and Environmental Factors in Coronary Atherosclerosis) study, who underwent coronary angiography between 1999 and 2001, we determined the incidence of CV death at follow-up. The eNOS T(-786)C and the exon 7 G(894)T SNPs were determined by melting curve analysis of amplicons from allele-specific fluorescence resonance energy transfer probes. Plasma levels of nitrate/nitrite, nitrotyrosine, and myeloperoxidase were also measured. The Kaplan-Meier and Cox regression analyses were used to assess the impact of SNPs on event-free survival. RESULTS:Complete follow-up data were obtained in 1,086 (98%) patients. After a median follow-up of 1,296 days (range 4 to 2,057 days), we observed 85 (8.2%) CV deaths. There was a significant impact of the T(-786)C eNOS genotype on CV death-free (p = 0.0102) survival, but no differences in CV death rates across G(894)T genotypes. The TT individuals, who showed a lower survival, exhibited higher plasma myeloperoxidase (p < 0.0001) and lower levels of nitrotyrosine (p < 0.0001) than CC patients. CONCLUSIONS:The T(-786)C SNP in the promoter of eNOS bears independent prognostic information and is associated with changes in markers of oxidant stress in high-risk white patients referred for coronary angiography.
journal_name
J Am Coll Cardioljournal_title
Journal of the American College of Cardiologyauthors
Rossi GP,Maiolino G,Zanchetta M,Sticchi D,Pedon L,Cesari M,Montemurro D,De Toni R,Zavattiero S,Pessina ACdoi
10.1016/j.jacc.2006.05.046subject
Has Abstractpub_date
2006-09-19 00:00:00pages
1166-74issue
6eissn
0735-1097issn
1558-3597pii
S0735-1097(06)01672-Xjournal_volume
48pub_type
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journal_title:Journal of the American College of Cardiology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
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更新日期:2010-01-26 00:00:00
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更新日期:1991-03-15 00:00:00
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更新日期:2019-11-12 00:00:00
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更新日期:1990-11-01 00:00:00
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更新日期:1989-05-01 00:00:00
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更新日期:2019-05-07 00:00:00
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更新日期:2018-06-19 00:00:00
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更新日期:2007-04-10 00:00:00