T-786-->C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm.
نویسندگان
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.
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....
متن کاملAssociation between T-786C polymorphism of endothelial nitric oxide synthase gene and level of the vessel dilation factor in patients with coronary artery disease
Various polymorphisms on endothelial nitric oxide synthase (eNOs) gene cause reduced production of NO, the endothelial relaxing factor, and may accelerate the process of atherosclerosis. The study designed to investigate the frequency of T-786C polymorphism of the eNOs gene in patients suffering from coronary artery disease (CAD) in north-west of Iran. One hundred twenty subjects including 60 p...
متن کاملRetraction Note: Association between T-786C polymorphism of endothelial nitric oxide synthase gene and level of the vessel dilation factor in patients with coronary artery disease
متن کامل
The relationship between insulin resistance and polymorphisms of the endothelial nitric oxide synthase gene in patients with coronary artery disease.
Nitric oxide (NO) regulates endothelial function and is believed to prevent atherogenesis. In endothelial cells, endothelial nitric oxide synthase (eNOS) is expressed constitutively, and regulates NO synthesis. A mutation of the eNOS gene has been associated with the development of coronary artery disease (CAD). The development of CAD is also influenced by insulin resistance, and recent studies...
متن کاملP-235: No Association of Endothelial Nitric Oxide Synthase (eNOS) -786T/C Polymorphism with Unexplained Recurrent Abortion in Iranian Women
Background: This is a case-control study to determine the relationship between endothelial nitric oxide synthase (eNOS) gene -786T/C polymorphism in women with unexplaiend recurrent abortion in comparison with healty women.Materials and Methods: 95 women with history of at least 2 unexplaiend recurrent abortion in the reproductive age range 20-35 years as patients group and 95 healty women (age...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Circulation
دوره 99 22 شماره
صفحات -
تاریخ انتشار 1999