The Endothelial Nitric Oxide Synthase Gene Is Associated with Coronary Artery Disease: A Meta-Analysis

Abstract

Introduction: Previous case-control studies have suggested that the endothelial nitric oxide synthase (eNOS) gene polymorphisms (G894T, 4b/a, T-786C) are associated with coronary artery disease (CAD). However, other studies do not confirm these relationships. The objective was to assess these relationships using meta-analysis. Methods: Databases, including Pubmed and Embase, were searched to access the relevant genetic association studies up to July 2009. Results: The meta-analysis included 56 studies, consisting of 23 studies for G894T, 19 for 4b/a and 14 for T-786C. For the allelic analysis of the G894T variant, all studies showed a positively significant association (OR = 0.83, p = 0.004). For the genotypic analysis, the combined studies of the T allele showed significance (OR = 1.57, p = 0.003). For the allelic analysis of the T-786C variant, all studies showed an obviously significant association (OR = 0.79, p = 0.0007), reflected in both non-Asian and Asian studies. For the genotype analysis, combined studies of the C allele showed significance (OR = 0.72, p = 0.0001). Moreover, non-Asian studies showed significant results. For the analysis of the 4b/a variant, none of the studies showed significant results. No publication bias was found in the meta-analysis. Conclusion: The synthesis of available evidence supports the fact that eNOS G894T andT-786C are associated with CAD.

Association between the endothelial nitric oxide synthase gene Glu298Asp polymorphism and coronary heart disease: A meta-analysis of 39 case-control studies

“…A polymorphic variant of this gene in exon 7 characterized by a Glu298Asp (894G→T) polymorphism has been identified. Although the mechanism responsible for the eNOS Glu298Asp mutation that is related to endothelial dysfunction remains unknown, various studies (8,9,(54)(55)(56)(57) have determined the correlation of its genotypes and numerous associated diseases. A number of studies have identified a lower Asp allele frequency in CHD cases than in healthy controls, as the two alleles are considered to have codominant effects on eNOS levels.…”

“…In contrast, the the MI and PCR-SSCP subgroup showed no association with the eNOS Glu298Asp polymorphism. Compared with a previous meta-analysis (8), the strength of the present meta-analysis was based on a more comprehensive search and the identification of a greater number of published studies, thereby providing more statistical power to detect the genetic effect estimates. A further sensitivity analysis confirmed that there was a significant association between the eNOS Glu298Asp polymorphism and the CHD risk among the Asian population.…”

“…In 2010, Li et al (8) performed a meta-analysis of 20 studies involving a non-Asian population and 3 studies involving an Asian population in order to detect the eNOS gene Glu298Asp polymorphism and risk of CHD. A significant association was found between the Asp (T) allele in the eNOS Glu298Asp (G894T) polymorphism and CHD in the non-Asian population, but not in the Asian population.…”

Clinical aspects of endothelial NO-synthase gene polymorphism in professional sportsmen (literature review)

“…Активація eNOS і підвищення рівня NO спостерігаються й під впливом агоністів кальцію, а також розтягування стінки судини, руху крові та деяких інших чинників [20]. Ферменти NO-синтази, зокрема eNOS, здатні утворювати не тільки оксид азоту, але й метабо-літи оксидантного стресу: іон супероксиду та пероксид С. М. Малахова водню, а також нітрит-аніон, особливо в умовах нестачі коферментів або аргініну [24]. Отже, ферменти синтезу NO слід розглядати як складний ферментний комплекс, що синтезує різноманітні високоактивні сполуки залежно від змін функціонального стану клітини, забезпеченості її коферментами, незамінними амінокислотами та анти-оксидантами.…”

Influence of Endothelial Nitric Oxide Synthase Gene Intron-4 27bp Repeat Polymorphism on Its Expression in Autoimmune Diseases

“…The eNOS gene consists of 26 exons located on chromosome 7q36.1. It has been extensively studied in various ethnic populations for its association with several cardiovascular diseases [14][15][16][17]. Numerous single nucleotide polymorphisms and variable number tandem repeats (VNTRs) have been reported in the eNOS gene, some of which may affect gene expression, protein synthesis and enzymatic activity, including T-786C, located in the promoter region, Glu298Asp, located in exon 7, and a VNTR of 27 bp in intron 4.…”