Endothelial Nitric Oxide Synthase Gene Polymorphisms and Risk of Coronary Artery Disease

Abstract

Background: Endothelial nitric oxide synthase (eNOS) could be a candidate gene for coronary artery disease (CAD). This study investigated the relationship of the eNOS Glu 298 3 Asp and T 786 3 C polymorphisms with the presence and severity of CAD in the Italian population. Methods: We enrolled 415 unrelated individuals who underwent coronary angiography. The severity of CAD was expressed by means of the Duke score. The eNOS Glu 298 3 Asp and T 786 3 C variants were analyzed by PCR. Results: There was significant linkage disequilibrium between the two eNOS polymorphisms (P <0.0001). Both variants were significantly associated with the occurrence and severity of CAD (P ‫؍‬ 0.01 and 0.004 for Glu 298 3 Asp and T 786 3 C, respectively). The risk of CAD was increased among individuals homozygous for the C allele of the T 786 3 C polymorphism compared with individuals homozygous for the T allele (odds ratio ‫؍‬ 2.5; P <0.01) and was independent of the other common risk factors (P ‫؍‬ 0.04). Moreover, individuals with both the Asp/Asp genotype of the Glu 298 3 Asp polymorphism and at least one C allele of the T 786 3 C variant in the promoter region of the eNOS gene had an increased risk of CAD (odds ratio ‫؍‬ 4.0; P <0.001) and a significantly higher mean Duke score (26.2 ؎ 2.9 vs 45.2 ؎ 3.7; P ‫؍‬ 0.002) compared with individuals with the TT genotype and the Glu allele. Conclusions:The present study provides evidence that the Glu 298 3 Asp and T 786 3 C polymorphisms of the eNOS gene are associated with the presence and sever-

Association of Endothelial Nitric Oxide Synthase Gene Polymor-phisms with Early-Onset Ischemic Stroke in South Indians

“…There are reports of linkage disequilibrium amongst variants of the gene 15,16,35,36) . Haplotype-specific co-ordination between promoter (T-786C) and intronic (4ab) variants of the gene has been shown to regulate its expression pattern in vitro 37) .…”

T-786C variation in the promoter sequence of human <i>eNOS</i> gene markedly influences its expression level

“…A statistically significant decrease in average eNOS expression has been reported for the T-786C polymorphism and was suggested to contribute to the vascular, contractile, and autonomic responses in failing human myocardium (6). Another study provided evidence that the same SNP is associated with the presence and severity of angiographically defined CAD in the Italian population (7).…”

Stratification of ST-elevation myocardial infarction patients based on soluble CD40L longitudinal changes

“…Genomic DNA was extracted from peripheral blood cells collected in EDTA tubes using a PureLink Genomic DNA Mini Kit (Invitrogen). A region containing each polymorphism 15 was amplified by polymerase chain reaction (PCR) using 1 mg of DNA and 1 mM of specific primers. Amplicons were then digested with specific restriction enzymes, and the digested fragments were visualized in a 2% ethidium bromide agarose gel.…”

“…16 T786C polymorphism result in a replacement of thymine by cytosine at nucleotide-786 position, decreasing transcription of eNOS gene and reducing in half the promoter activity. 15 MicroRNA quantification analysis. RNA was extracted from serum samples using miRCURY RNA Isolation Kit (Exiqon).…”