T-786-->C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm.

نویسندگان

  • M Nakayama
  • H Yasue
  • M Yoshimura
  • Y Shimasaki
  • K Kugiyama
  • H Ogawa
  • T Motoyama
  • Y Saito
  • Y Ogawa
  • Y Miyamoto
  • K Nakao
چکیده

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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منابع مشابه

Response to renin-angiotensin system antagonists in hypertensive black subjects.

1. Rossi GP, Cesari M, Zanchetta M, et al. The TC endothelial nitric oxide synthase genotype is a novel risk factor for coronary artery disease in Caucasian patients of the GENICA study. J Am Coll Cardiol 2003;41:930–7. 2. Alvarez R, Gonzalez P, Batalla A, et al. Association between the NOS3 (-786 T/C) and the ACE (I/D) DNA genotypes and early coronary artery disease. Nitric Oxide 2001;5:343–8....

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عنوان ژورنال:
  • Circulation

دوره 99 22  شماره 

صفحات  -

تاریخ انتشار 1999