Influence of endothelial nitric oxide synthase gene polymorphisms (G894T, 4a4b, T-786C) and hyperhomocysteinemia on the predisposition to acute coronary syndromes

Cinzia Fatini, Francesco Sofi, Elena Sticchi, Francesca Gensini, Anna Maria Gori, Sandra Fedi, Ilaria Lapini, Carlo Rostagno, Marco Comeglio, Daria Brogi, Gianfranco Gensini, Rosanna Abbate

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Abstract

Background Nitric oxide is an endothelium-derived relaxing factor that contributes significantly to vascular tone regulation. In this study we investigated the role of endothelial nitric oxide synthase (eNOS) polymorphisms as predisposing factors to acute coronary syndromes (ACS). Methods In 477 consecutive patients admitted to the coronary intensive therapy unit of the University of Florence and in 537 unrelated controls, genotypes of eNOS G894T and T-786C polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism analysis and the repeat polymorphism 4a/4b was analyzed by polymerase chain reaction. The genotype distribution was in Hardy-Weinberg equilibrium for all variants. Results The multivariate analysis showed that the homozygosity for the eNOS 4a rare variant represented an independent predisposition factor to ACS (odds ratio [OR] 2.5, 95% CI 1.1-5.4, P = .02) and in particular influenced the risk of acute myocardial infarction (OR 3.6, 95% CI 1.2-11.5, P = .03). Subjects carrying the 4a4a/-786CC haplotype showed a higher predisposition to the disease (OR 6.1, 95% CI 1.3-29.6, P = .02). The contemporary presence of hyperhomocysteinemia and homozygosity for the -786C variant influenced the predisposition to ACS (OR 9.1, 95% CI 1.7-46.7, P = .008). Conclusions The presence of the eNOS 4a4a genotype represents a predisposing condition to ACS and in particular to acute myocardial infarction. Moreover, our data provide the evidence that the -786CC pattern modulates the susceptibility to ACS in 4a4a homozygotes and in hyperhomocysteinemic patients.

Original languageEnglish
Pages (from-to)516-521
Number of pages6
JournalAmerican Heart Journal
Volume147
Issue number3
DOIs
Publication statusPublished - Mar 2004

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Hyperhomocysteinemia
Nitric Oxide Synthase Type III
Acute Coronary Syndrome
Odds Ratio
Genes
Genotype
Myocardial Infarction
Endothelium-Dependent Relaxing Factors
Polymerase Chain Reaction
Homozygote
Restriction Fragment Length Polymorphisms
Causality
Haplotypes
Blood Vessels
Nitric Oxide
Multivariate Analysis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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Influence of endothelial nitric oxide synthase gene polymorphisms (G894T, 4a4b, T-786C) and hyperhomocysteinemia on the predisposition to acute coronary syndromes. / Fatini, Cinzia; Sofi, Francesco; Sticchi, Elena; Gensini, Francesca; Gori, Anna Maria; Fedi, Sandra; Lapini, Ilaria; Rostagno, Carlo; Comeglio, Marco; Brogi, Daria; Gensini, Gianfranco; Abbate, Rosanna.

In: American Heart Journal, Vol. 147, No. 3, 03.2004, p. 516-521.

Research output: Contribution to journalArticle

Fatini, C, Sofi, F, Sticchi, E, Gensini, F, Gori, AM, Fedi, S, Lapini, I, Rostagno, C, Comeglio, M, Brogi, D, Gensini, G & Abbate, R 2004, 'Influence of endothelial nitric oxide synthase gene polymorphisms (G894T, 4a4b, T-786C) and hyperhomocysteinemia on the predisposition to acute coronary syndromes', American Heart Journal, vol. 147, no. 3, pp. 516-521. https://doi.org/10.1016/j.ahj.2003.10.032
Fatini, Cinzia ; Sofi, Francesco ; Sticchi, Elena ; Gensini, Francesca ; Gori, Anna Maria ; Fedi, Sandra ; Lapini, Ilaria ; Rostagno, Carlo ; Comeglio, Marco ; Brogi, Daria ; Gensini, Gianfranco ; Abbate, Rosanna. / Influence of endothelial nitric oxide synthase gene polymorphisms (G894T, 4a4b, T-786C) and hyperhomocysteinemia on the predisposition to acute coronary syndromes. In: American Heart Journal. 2004 ; Vol. 147, No. 3. pp. 516-521.
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abstract = "Background Nitric oxide is an endothelium-derived relaxing factor that contributes significantly to vascular tone regulation. In this study we investigated the role of endothelial nitric oxide synthase (eNOS) polymorphisms as predisposing factors to acute coronary syndromes (ACS). Methods In 477 consecutive patients admitted to the coronary intensive therapy unit of the University of Florence and in 537 unrelated controls, genotypes of eNOS G894T and T-786C polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism analysis and the repeat polymorphism 4a/4b was analyzed by polymerase chain reaction. The genotype distribution was in Hardy-Weinberg equilibrium for all variants. Results The multivariate analysis showed that the homozygosity for the eNOS 4a rare variant represented an independent predisposition factor to ACS (odds ratio [OR] 2.5, 95{\%} CI 1.1-5.4, P = .02) and in particular influenced the risk of acute myocardial infarction (OR 3.6, 95{\%} CI 1.2-11.5, P = .03). Subjects carrying the 4a4a/-786CC haplotype showed a higher predisposition to the disease (OR 6.1, 95{\%} CI 1.3-29.6, P = .02). The contemporary presence of hyperhomocysteinemia and homozygosity for the -786C variant influenced the predisposition to ACS (OR 9.1, 95{\%} CI 1.7-46.7, P = .008). Conclusions The presence of the eNOS 4a4a genotype represents a predisposing condition to ACS and in particular to acute myocardial infarction. Moreover, our data provide the evidence that the -786CC pattern modulates the susceptibility to ACS in 4a4a homozygotes and in hyperhomocysteinemic patients.",
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T1 - Influence of endothelial nitric oxide synthase gene polymorphisms (G894T, 4a4b, T-786C) and hyperhomocysteinemia on the predisposition to acute coronary syndromes

AU - Fatini, Cinzia

AU - Sofi, Francesco

AU - Sticchi, Elena

AU - Gensini, Francesca

AU - Gori, Anna Maria

AU - Fedi, Sandra

AU - Lapini, Ilaria

AU - Rostagno, Carlo

AU - Comeglio, Marco

AU - Brogi, Daria

AU - Gensini, Gianfranco

AU - Abbate, Rosanna

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Y1 - 2004/3

N2 - Background Nitric oxide is an endothelium-derived relaxing factor that contributes significantly to vascular tone regulation. In this study we investigated the role of endothelial nitric oxide synthase (eNOS) polymorphisms as predisposing factors to acute coronary syndromes (ACS). Methods In 477 consecutive patients admitted to the coronary intensive therapy unit of the University of Florence and in 537 unrelated controls, genotypes of eNOS G894T and T-786C polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism analysis and the repeat polymorphism 4a/4b was analyzed by polymerase chain reaction. The genotype distribution was in Hardy-Weinberg equilibrium for all variants. Results The multivariate analysis showed that the homozygosity for the eNOS 4a rare variant represented an independent predisposition factor to ACS (odds ratio [OR] 2.5, 95% CI 1.1-5.4, P = .02) and in particular influenced the risk of acute myocardial infarction (OR 3.6, 95% CI 1.2-11.5, P = .03). Subjects carrying the 4a4a/-786CC haplotype showed a higher predisposition to the disease (OR 6.1, 95% CI 1.3-29.6, P = .02). The contemporary presence of hyperhomocysteinemia and homozygosity for the -786C variant influenced the predisposition to ACS (OR 9.1, 95% CI 1.7-46.7, P = .008). Conclusions The presence of the eNOS 4a4a genotype represents a predisposing condition to ACS and in particular to acute myocardial infarction. Moreover, our data provide the evidence that the -786CC pattern modulates the susceptibility to ACS in 4a4a homozygotes and in hyperhomocysteinemic patients.

AB - Background Nitric oxide is an endothelium-derived relaxing factor that contributes significantly to vascular tone regulation. In this study we investigated the role of endothelial nitric oxide synthase (eNOS) polymorphisms as predisposing factors to acute coronary syndromes (ACS). Methods In 477 consecutive patients admitted to the coronary intensive therapy unit of the University of Florence and in 537 unrelated controls, genotypes of eNOS G894T and T-786C polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism analysis and the repeat polymorphism 4a/4b was analyzed by polymerase chain reaction. The genotype distribution was in Hardy-Weinberg equilibrium for all variants. Results The multivariate analysis showed that the homozygosity for the eNOS 4a rare variant represented an independent predisposition factor to ACS (odds ratio [OR] 2.5, 95% CI 1.1-5.4, P = .02) and in particular influenced the risk of acute myocardial infarction (OR 3.6, 95% CI 1.2-11.5, P = .03). Subjects carrying the 4a4a/-786CC haplotype showed a higher predisposition to the disease (OR 6.1, 95% CI 1.3-29.6, P = .02). The contemporary presence of hyperhomocysteinemia and homozygosity for the -786C variant influenced the predisposition to ACS (OR 9.1, 95% CI 1.7-46.7, P = .008). Conclusions The presence of the eNOS 4a4a genotype represents a predisposing condition to ACS and in particular to acute myocardial infarction. Moreover, our data provide the evidence that the -786CC pattern modulates the susceptibility to ACS in 4a4a homozygotes and in hyperhomocysteinemic patients.

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