Genetic and Environmental Determinants of Plasma Nitrogen Oxides and Risk of Ischemic Heart Disease

Jeerooburkhan, Noor; Jones, Lyle V.; Bujac, Sarah R.; Cooper, Jacqueleine A.; Miller, George; Vallance, Patrick; Humphries, Steve E.; Hingorani, Aroon D.

doi:10.1161/hy1101.092967

Cited by 109 publications

(81 citation statements)

References 53 publications

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“…The allelic frequencies in our control group were in agreement with other studies, [43][44][45][46] and the linkage disequilibrium between the T-786C and E298D polymorphisms also confirmed previous reports. 46,47 The single locus findings were confirmed by the results of our 2-locus genotype analysis, with a lower risk for POTS in individuals homozygous for -786C and 298D, based on OR and 95% CI. Although haplotype analysis also indicated a significant difference between the POTS and control groups, we chose to focus on the results of genotype analyses, which are more biologically meaningful.…”

Section: Discussionsupporting

confidence: 93%

Endothelial NO Synthase Polymorphisms and Postural Tachycardia Syndrome

et al. 2005

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Abstract-Postural tachycardia syndrome (POTS) is a heterogeneous disorder characterized by an excessive rise in heart rate and symptoms consistent with cerebral hypoperfusion in the upright position. NO produced by endothelial NO synthase is a significant factor in the regulation of blood flow. Genetic polymorphisms in the promoter region (T-786C) and exon 7 (E298D) of the NO synthase isoform 3 gene affect enzyme activity and have been associated with a number of cardiovascular diseases. Because some findings in POTS suggest aberrant NO-mediated functions, we postulated that the variant genotypes of these polymorphisms may increase the risk of developing POTS and correlate with more severe symptoms. We genotyped 136 patients with POTS (mean age 32.2Ϯ9.9 years; 46 men and 90 women) from Nashville, Tenn, and Vienna, Austria, and compared them with 191 healthy volunteers (mean age 29.1Ϯ8.0 years; 127 men and 64 women). Participants also underwent orthostatic testing with blood pressure, heart rate, and plasma norepinephrine measurements while supine and upright.

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Section: Discussionsupporting

confidence: 93%

Endothelial NO Synthase Polymorphisms and Postural Tachycardia Syndrome

et al. 2005

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“…Furthermore, another association study between genetic polymorphisms of the eNOS gene and hypertension in Japanese has recently shown that the T 786 3 C polymorphism is significantly linked to the Glu 298 3 Asp polymorphism with trans configuration (the T 786 allele is linked to the Asp 298 and the C 786 allele to the Glu 298 ) (24 ). In this study we found that the Asp 298 allele is weakly but significantly linked to the C 786 allele of the T 786 3 C polymorphism in the 5Ј-flanking region of the eNOS gene; this evidence is in agreement with that recently reported in another European population in terms of both extent of disequilibrium and allele frequency (25 ).…”

Section: Discussionsupporting

confidence: 93%

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

Colombo¹,

Paradossi²,

Andreassi³

et al. 2003

Clinical Chemistry

151

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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-

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“…Other investigators previously found the eNOS Glu298Asp polymorphism to be related to the presence of atherosclerotic manifestations such as coronary artery disease 29 -31 and carotid atherosclerotic plaques, 32 although negative reports have also been published. 28 Because atherosclerotic renovascular disease is generally viewed as a local manifestation of systemic atherosclerotic disease, at least our data in ARASϩ are in line with these earlier observations. Even the results in ARASϪ patients may be compatible with more severe atherosclerosis in these individuals.…”

Section: Van Onna Et Al Candidate Genes In Renal Artery Disease 451supporting

confidence: 89%

Genetic Risk of Atherosclerotic Renal Artery Disease

et al. 2004

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Abstract-It is largely unknown to what extent genetic abnormalities contribute to the development of atherosclerotic renal artery disease. Among the potential candidate genes, those of the renin-angiotensin system and the endothelial nitric oxide synthase (eNOS) rank high because of their importance in the atherosclerotic process. We investigated the association of polymorphisms in these genes (the angiotensinogen Met235Thr, the angiotensin-converting enzyme insertion/deletion, the angiotensin II type-1 receptor A1166C, and the eNOS Glu298Asp) with the presence or absence of atherosclerotic renovascular disease in 456 consecutive hypertensive patients referred for renal angiography on the suspicion of renovascular hypertension. Nondiseased normotensive (nϭ200) and hypertensive (nϭ154) patients from a family practice served as external controls. Renal artery disease was present in 30% of our angiography group. The Asp allele of the eNOS Glu298Asp polymorphism was associated with atherosclerotic renal artery stenosis with an odds ratio of 1.44 (95% confidence interval 1.00 to 2.09) versus hypertensives with angiographically proven patent arteries, of 1.89 (1.24 to 2.87) versus hypertensive family practice controls, and of 2.09 (1.29 to 3.38) versus normotensive family practice controls. However, this allele also differed significantly between patients with patent renal arteries and normotensive and hypertensive controls. No differences were found with respect to the other genetic polymorphisms. We hypothesize that the Asp allele of the Glu298Asp polymorphism may predispose to the development of atherosclerotic lesions but that renal artery involvement depends on other factors, also.

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Genetic and Environmental Determinants of Plasma Nitrogen Oxides and Risk of Ischemic Heart Disease

Cited by 109 publications

References 53 publications

Endothelial NO Synthase Polymorphisms and Postural Tachycardia Syndrome

Endothelial NO Synthase Polymorphisms and Postural Tachycardia Syndrome

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

Genetic Risk of Atherosclerotic Renal Artery Disease

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