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T-786-->C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm.
Nakayama, M; Yasue, H; Yoshimura, M; Shimasaki, Y; Kugiyama, K; Ogawa, H; Motoyama, T; Saito, Y; Ogawa, Y; Miyamoto, Y; Nakao, K.
Afiliación
  • Nakayama M; Department of Cardiovascular Medicine, Kumamoto University School of Medicine, Japan.
Circulation ; 99(22): 2864-70, 1999 Jun 08.
Article en En | MEDLINE | ID: mdl-10359729
BACKGROUND: Coronary spasm plays an important role in the pathogenesis of ischemic heart diseases in general. However, the precise mechanism(s) responsible for coronary spasm remains to be elucidated, and we examined the molecular genetics of coronary spasm. METHODS AND RESULTS: We searched for the possible mutations in the endothelial nitric oxide synthase (eNOS) gene in patients with coronary spasm. In this study, we demonstrate the existence of 3 linked mutations in the 5'-flanking region of the eNOS gene (T-786-->C, A-922-->G, and T-1468-->A). The incidence of the mutations was significantly greater in patients with coronary spasm than in the control group (P<0.0001). Multiple logistic regression analysis with forward stepwise selection using the environmental risk factors and the eNOS gene variant revealed that the most predictive independent risk factor for coronary spasm was the mutant allele (P<0.0001). As assessed by luciferase reporter gene assays, the T-786-->C mutation resulted in a significant reduction in eNOS gene promoter activity (P<0.05), whereas neither the A-922-->G nor the T-1468-->A mutation had any affect. CONCLUSIONS: Taken together, these findings strongly suggest that the T-786-->C mutation in the eNOS gene reduces the endothelial NO synthesis and predisposes the patients with the mutation to coronary spasm.
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Banco de datos: MEDLINE Asunto principal: Óxido Nítrico Sintasa / Vasoespasmo Coronario / Mutación Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Circulation Año: 1999 Tipo del documento: Article País de afiliación: Japón
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Banco de datos: MEDLINE Asunto principal: Óxido Nítrico Sintasa / Vasoespasmo Coronario / Mutación Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Circulation Año: 1999 Tipo del documento: Article País de afiliación: Japón