Endothelial Nitric Oxide Synthase Gene Polymorphism and Acute Myocardial Infarction

Abstract

Abstract-Recently a point mutation of guanine to thymine at nucleotide position 1917 in the endothelial nitric oxide synthase (eNOS) gene has been reported to be associated with coronary artery spasm. In addition, a significant association of the 4a/b polymorphism in intron 4 of the eNOS gene with coronary artery disease has been reported. However, the implications of these polymorphisms with respect to acute myocardial infarction (AMI) remain to be established. We conducted a case-control study of 226 patients with AMI and 357 healthy gender-and age-matched control subjects. In the former group, coronary angiograms were evaluated according to angiographic criteria based on the number of diseased vessels (Ն75%) and the number of stenotic lesions (Ն50%). Homozygosity for the Glu-Asp298 polymorphism existed in 5 of 226 patients with AMI (2.2%) but not in any of the 357 control subjects (Pϭ.0085). However, when we evaluated the coronary angiograms of 226 case patients, there was no difference in the number of diseased vessels or the number of stenotic lesions between the patients with this homozygote and those without it. By contrast, there was no evidence of a significant increase in the risk of AMI or the severity of coronary atherosclerosis among individuals with the a/a genotype of the eNOS4a/b polymorphism. Our results imply that patients who are homozygous for the Glu-Asp298 polymorphism may be genetically predisposed to AMI; however, this mutation apparently is not related to the severity of coronary atherosclerosis. Further studies are needed to confirm our results and characterize the molecular mechanisms by which eNOS is involved in susceptibility to AMI. (Hypertension. 1998;32:521-526.)Key Words: endothelium-derived relaxing factor Ⅲ genes Ⅲ myocardial infarction Ⅲ atherosclerosis Ⅲ angiography S ince the identification of nitric oxide (NO) as an important endothelium-derived relaxing factor, there has been an explosion of new information on the physiological and pathophysiological roles of NO. NO is synthesized from the amino acid L-arginine by a family of enzymes, referred to as NO synthase (NOS). Three distinct isoforms of NOS have been identified to date.1 The inducible NOS is expressed in vessel walls and macrophages by certain cytokines and endotoxin lipopolysaccharides in pathological conditions. 2The constitutive neuronal NOS is expressed in the central and peripheral nervous systems as well as in macula densa of kidney. It plays important roles in physiological 3 and pathophysiological 4 conditions. The constitutive endothelial NO synthase (eNOS) is expressed in the endothelium, where it produces NO from L-arginine. NO diffuses from the endothelium to the vascular smooth muscle cells, where it increases the concentration of cGMP by stimulating soluble guanylate cyclase, leading to vascular relaxation.

Endothelial nitric oxide synthase polymorphism, nitric oxide production, salt sensitivity and cardiovascular risk factors in Hispanics

“…9,12,13,23,26,34,35 The frequency of the T allele in Venezuelans was comparable to that described for Caucasians, since the T allele was found in 30% of the Venezuelan subjects studied (present study).…”

“…The missense Glu298Asp variant has been correlated with increased incidence of coronary spasm, 31 coronary heart disease, 22 myocardial infarction, 12 essential hypertension, 9,11 left ventricular hypertrophy, carotid atherosclerosis and cerebral infarction. 48 Whereas in other studies, no association between 298Asp with coronary artery disease, [22][23][24][25] essential hypertension, [17][18][19][20][21] left ventricular hypertrophy and carotid atherosclerosis 17,35 and cerebrovascular disease 29,49 was observed.…”

Association of - 786T-C mutation of endothelial nitric oxide synthase gene with insulin resistance

“…In this study we assessed IMT as an index of early atherosclerosis. There are several reports showing the association of Glu298Asp polymorphism and myocardial infarction [25,41,42]. On the other hand, there are inconsistencies according to European reports examining the association of Glu298Asp polymorphism and carotid atherosclerosis [43,44], and there has been no report about the association of -786T-C polymorphism and carotid atherosclerosis.…”

Association between eNOS polymorphisms and risk of coronary artery disease in a Korean population: a meta-analysis

“…This variant was suggested to be a contributing factor for coronary spasm, acute myocardial infarction, and the development of CAD (Hibi et al, 1998;Shimasaki et al, 1998;Yoshimura et al, 1998;Hingorani et al, 1999;Colombo et al, 2002Colombo et al, , 2003. eNOS 894G>T is also a genetic risk factor for in-stent restenosis (Suzuki et al, 2002).…”