Endothelial Nitric Oxide Synthase (eNOS)T-786C Mutation
Nitric oxide plays an important role in maintaining vascular tone. A
deficiency in its synthesis may predispose individuals to very serious
coronary vascular disorders, such as coronary spasm, angina pectoris
and myocardial infarction. eNOS catalyses the synthesis of nitric oxide.
Presence of a T-786C mutation in the eNOS gene results in decreased
synthesis of nitric oxide and confers a 3-fold greater risk for coronary
spasm. Since coronary spasm is difficult to diagnose, screening for this
eNOS mutation in families with risk for coronary artery disease would
enable early and appropriate therapy. Patients carrying the T-786C
mutation should be strongly cautioned against tobacco smoking. The
incidence of tobacco smoke induced Buerger's disease, otherwise knows
as thromboangiitis obliterans, is 1 per 8,000 people.
Scientific Articles on eNOS. Free PDF copies of some of these articles can be
obtained from PubMed at NCBI (National Center for Biotechnology Information):
Ghilardi G, Biondi ML, DeMonti M, Bernini M, Turri O, Massaro F, Guagnellini E,
Scorza R. Independent risk factor for moderate to severe internal carotid artery
stenosis: T786C mutation of the endothelial nitric oxide synthase gene.
Clin Chem. 2002 Jul;48(7):989-93. Free pdf copy.
Rossi GP, Cesari M, Zanchetta M, Colonna S, Maiolino G, Pedon L, Cavallin M,
Maiolino P, Pessina AC. The T-786C 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 Mar 19;41(6):930-7.
Nakayama M, Yoshimura M, Sakamoto T, Shimasaki Y, Nakamura S, Ito T, Abe
K, Yamamuro M, Miyamoto Y, Saito Y, Nakao K, Yasue H, Ogawa H.
Synergistic interaction of T-786-->C polymorphism in the endothelial nitric oxide
synthase gene and smoking for an enhanced risk for coronary spasm.
Pharmacogenetics. 2003 Nov;13(11):683-8.
Yoshimura M, Nakayama M, Shimasaki Y, Ogawa H, Kugiyama K, Nakamura
S, Ito T, Mizuno Y, Harada E, Yasue H, Miyamoto Y, Saito Y, Nakao K. A
T-786-->C mutation in the 5'-flanking region of the endothelial nitric oxide
synthase gene and coronary arterial vasomotility. Am J Cardiol. 2000 Mar
Miyamoto Y, Saito Y, Nakayama M, Shimasaki Y, Yoshimura T, Yoshimura M,
Harada M, Kajiyama N, Kishimoto I, Kuwahara K, Hino J, Ogawa E, Hamanaka
I, Kamitani S, Takahashi N, Kawakami R, Kangawa K, Yasue H, Nakao K.
Replication protein A1 reduces transcription of the endothelial nitric oxide
synthase gene containing a -786T-->C mutation associated with coronary
spastic angina. Hum Mol Genet. 2000 Nov 1;9(18):2629-37.
Nakayama M, Yasue H, Yoshimura M, Shimasaki Y, Ogawa H, Kugiyama K,
Mizuno Y, Harada E, Nakamura S, Ito T, Saito Y, Miyamoto Y, Ogawa Y, Nakao
K. T(-786)--> C mutation in the 5'-flanking region of the endothelial nitric oxide
synthase gene is associated with myocardial infarction, especially without
coronary organic stenosis. Am J Cardiol. 2000 Sep 15;86(6):628-34.
Nakayama M, Yasue H, Yoshimura M, Shimasaki Y, Kugiyama K, Ogawa H,
Motoyama T, Saito Y, Ogawa Y, Miyamoto Y, Nakao K. T-786-->C mutation in
the 5'-flanking region of the endothelial nitric oxide synthase gene is associated
with coronary spasm. Circulation. 1999 Jun 8;99(22):2864-70. Free pdf copy:
Barbera JA, Peinado VI, Santos S, Ramirez J, Roca J, Rodriguez-Roisin R.
Reduced expression of endothelial nitric oxide synthase in pulmonary arteries of
smokers. Am J Respir Crit Care Med. 2001 Aug 15;164(4):709-13.
Free pdf copy:
Barua RS, Ambrose JA, Eales-Reynolds LJ, DeVoe MC, Zervas JG, Saha DC.
Dysfunctional endothelial nitricoxide biosynthesis in healthy smokers with
impaired endothelium-dependent vasodilatation. Circulation. 2001 Oct
16;104(16):1905-10. Free pdf copy.
Barua RS, Ambrose JA, Srivastava S, DeVoe MC, Eales-Reynolds LJ. Reactiveoxygen species are involved in smoking-induced dysfunction of nitric oxide
biosynthesis and upregulation of endothelial nitric oxide synthase: an in vitro
demonstration in human coronary artery endothelial cells. Circulation. 2003 May
13;107(18):2342-7. Free pdf copy.
Barua RS, Ambrose JA, Saha DC, Eales-Reynolds LJ. Smoking is associated
with altered endothelial-derived fibrinolytic and antithrombotic factors: an in vitro
demonstration. Circulation. 2002 Aug 20;106(8):905-8. Free pdf copy.
Nasreen S, Nabika T, Shibata H, Moriyama H, Yamashita K, Masuda J,
Kobayashi S. T-786C polymorphism in endothelial NO synthase gene affects
cerebral circulation in smokers: possible gene-environmental interaction.
Arterioscler Thromb Vasc Biol. 2002 Apr 1;22(4):605-10. Free pdf copy.
Wang J, Dudley D, Wang XL. Haplotype-specific effects on endothelial NO
synthase promoter efficiency: modifiable by cigarette smoking. Arterioscler
Thromb Vasc Biol. 2002 May 1;22(5):e1-4.
Perez-Ruiz A, Montes R, Velasco F, Lopez-Pedrera C, Antonio Paramo J, Orbe
J, Hermida J, Rocha E. Regulation by nitric oxide of endotoxin-induced tissue
factor and plasminogen activator inhibitor-1 in endothelial cells. Thromb
Haemost. 2002 Dec;88(6):1060-5.
Articles on Stromelysin-1 (aka, MMP3)
Liu PY, Chen JH, Li YH, Wu HL, Shi GY. Synergistic effect of stromelysin-1
(matrix metallo-proteinase-3) promoter 5A/6A polymorphism with smoking on the
onset of young acute myocardial infarction. Thromb Haemost. 2003
Humphries SE. The stromelysin-1 (MMP-3) gene and risk of coronary artery
disease: a candidate gene that has won the election? Thromb Haemost. 2003