G894T Polymorphism in the Endothelial Nitric Oxide Synthase Gene Is Associated With an Enhanced Vascular Responsiveness to Phenylephrine

Philip, Ivan; Plantefève, Gaëtan; Vuillaumier‐Barrot, Sandrine; Vicaut, Éric; Lemarié, Claude; Henrion, Didier; Poirier, Odette; Lévy, Bernard; Desmonts, J. M.; Durand, Geneviève; Bénessiano, Joëlle

doi:10.1161/01.cir.99.24.3096

Cited by 168 publications

(106 citation statements)

References 7 publications

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“…12 Tesauro and colleagues reported that eNOS isoforms are intracellularly processed differently depending on the presence of aspartate or glutamate at position 298, 11 and Pillip and coworkers revealed an enhanced vascular responsiveness to alpha-adrenergic stimulation in subjects with the 298Asp (894T) allele in the eNOS gene. 9 In this study, we observed that the frequency of 4a allele was significantly higher in FHON group, especially idiopathic osteonecrosis patients. The calculated statistical power was 0.824 for total patients and 0.892 for idiopathic FHON subgroup.…”

Section: Discussionmentioning

confidence: 53%

“…8 Furthermore, it was proposed that two polymorphic sites of the eNOS gene, the 27-bp repeat polymorphism in intron 4 and Glu298Asp polymorphism in exon 7, are related to each other and might be associated with the altered function of this gene. [9][10][11][12] The -786 T/C polymorphism is related with Glu298Asp polymorphism because two polymorphic sites lie in a gene and was also reported to be associated with eNOS gene function. Some reports showed that the -786 T/C polymorphism was significantly associated with cardiovascular diseases.…”

Section: Introductionmentioning

confidence: 99%

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Endothelial nitric oxide synthase gene polymorphisms in patients with nontraumatic femoral head osteonecrosis

Koo

Lee

et al. 2006

Journal Orthopaedic Research

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As endothelial nitric oxide synthase (eNOS) has beneficial effects on skeletal, vascular, and thrombotic systems, the association between nontraumatic femoral head osteonecrosis (FHON) and eNOS gene polymorphisms was investigated in Korean patients with FHON. Genomic DNA from 103 patients with nontraumatic FHON (idiopathic in 50, steroid-induced in 29, and alcohol abuse in 24) and 103 control subjects matched for gender and age (3-year range) was analyzed for the 27-bp repeat polymorphism in intron 4 and Glu298Asp polymorphism in exon 7. The frequencies of alleles and genotypes were compared between patients and control subjects. The frequency of 4a allele was significantly higher in total patients than control subjects [6.8% vs. 2.4%, p ¼ 0.0345, odds ratio (OR) 2.931]. In subgroup analysis, the 4a allele significantly increased in patients with idiopathic FHON versus control subjects (9.0% vs. 2.4%, p ¼ 0.0297, OR 3.976). The frequency of the 4a/b genotype in total patients (13.6% vs. 4.9%, p ¼ 0.0302, OR 3.083) as well as patients with idiopathic FHON (18.0% vs. 4.9%, p ¼ 0.0246, OR 4.302) was higher than control subjects. The distribution of Glu298Asp polymorphisms was not significantly different between patients and control subjects. Microstellate polymorphism in intron 4 of eNOS polymorphism was significantly associated with idiopathic FHON in Korean patients. Because 4a allele is associated with lower synthesis of eNOS, these results suggest that carrier state of 4a allele in intron 4 might be a genetic risk factor of FHON and could provide insight into the protective role of nitric oxide in the pathogenesis of FHON. ß

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Section: Discussionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Endothelial nitric oxide synthase gene polymorphisms in patients with nontraumatic femoral head osteonecrosis

Koo

Lee

et al. 2006

Journal Orthopaedic Research

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“…Furthermore, several recent studies have suggested that arterial mechanics are influenced by specific gene polymorphisms or combinations thereof. They may be divided into 2 categories: those related to the pathophysiology of high BP, such as the renin-angiotensin-aldosterone system, the endothelial NO synthase system, and the ␣-adducin systems, [43][44][45][46] and those related to CV aging, particularly those related to elastin, collagen, and telomere length. [47][48][49] However, results regarding the association of individual gene polymorphisms with arterial behavior are still controversial.…”

Section: Arterial Stiffness Cardiovascular Diseases and Genomic Conmentioning

confidence: 99%

Current Perspectives on Arterial Stiffness and Pulse Pressure in Hypertension and Cardiovascular Diseases

2003

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Blood pressure (BP) is a powerful cardiovascular (CV) risk factor that acts on the arterial wall and is responsible in part for various CV events, such as cerebrovascular accidents and ischemic heart disease. In clinical practice, 2 specific and arbitrary points of the BP curve, peak systolic BP (SBP) and end-diastolic BP (DBP), are used to define the CV risk factor. Because the goal of drug treatment of hypertension is to prevent CV complications, it appears likely that the totality of the BP curve, not simply 2 specific and arbitrary points, should be considered to act mechanically on the arterial wall and therefore should be used to propose an adequate definition of high BP.A current approach consists of considering the BP curve as the summation of a steady component, mean blood pressure (MBP), and a pulsatile component, pulse pressure (PP). 1 MBP, the product of cardiac output multiplied by total peripheral resistance, is the pressure for the steady flow of blood and oxygen to peripheral tissues and organs. The pulsatile component, PP, is the consequence of intermittent ventricular ejection from the heart. PP is influenced by several cardiac and vascular factors, but it is the role of large conduit arteries, mainly the aorta, to minimize pulsatility. In addition to the pattern of left ventricular ejection, the determinants of PP (and SBP) are the cushioning capacity of arteries and the timing and intensity of wave reflections. 1 The former is influenced by arterial stiffness, usually expressed in the quantitative terms of compliance and distensibility. 1 The latter result from the summation of a forward wave coming from the heart and propagating at a given speed (pulse wave velocity, or PWV) toward the origin of resistance vessels and a backward wave returning toward the heart from particular sites characterized by specific reflection coefficients. 1 Over the past few years, arterial stiffness and wave reflections have been widely investigated in old and/or hypertensive subjects for several reasons. First, whereas DBP was considered in the past as the better guide to determine disease severity, epidemiological studies have directed attention to SBP as a more informative CV risk factor, particularly in patients older than 50 years of age, and it has been shown that PP is an independent marker of CV risk, mainly for myocardial infarction. 2 Second, in subjects Ͼ50 years of age, ventricular ejection tends to be reduced, so that arterial stiffness and amplitude and timing of wave reflections become the main determinants of increased SBP and PP. Third, whereas drug control of DBP is consistently obtained in large populations of hypertensive patients, the ability to control SBP is observed much less frequently. 3 Finally, increased PP is also a predictor of CV risk in subjects with recurrent myocardial infarction and congestive heart failure. 2,4,5 From the hemodynamic factors that influence PP, 2 have been shown to independently predict CV risk: aortic stiffness, measured from aortic PWV, 6,7 and early return of...

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“…In contrast, the -786T-C mutation reduces the promoter activity [12] and thus reduces eNOS protein expression and eNOS activity [10]. Both Glu298Asp and -786T-C polymorphism have been reported to lead to abnormal vasomotility [13,14] and to be associated with vasoconstrictive angina [12,15]. However, the association between both eNOS polymorphisms and insulin resistance has not been found.…”

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confidence: 99%

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

et al. 2002

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Aims/hypothesis. Endothelial derived nitric oxide synthase (eNOS) gene polymorphisms affect eNOS activity and are associated with abnormal vasomotility and impaired local blood flow. A decrease in local blood flow has been reported to cause insulin resistance. The aim of this study was to examine a possible association of two eNOS polymorphisms, Glu298Asp (G894T) in exon 7 and -786T-C mutation with insulin resistance. Methods. Genotypes of both Glu298Asp and -786T-C mutation were examined by the PCR-RFLP method. Plasma nitrate and nitrite concentrations were also measured. Results. The allele frequencies of both polymorphisms showed no considerable differences in 233 non-diabetic subjects and 301 patients with Type II (non-insulin-dependent) diabetes mellitus. Non-diabetic subjects with the -786C allele had (p<0.05) higher fasting plasma insulin and homeostasis model assessment of insulin resistance than those with the -786T/ -786T genotype. Diabetic subjects with -786C allele showed higher HbA 1c than those with the -786T/ -786T genotype. A euglycaemic hyperinsulinemic clamp study done on 71 of the 301 patients showed a lower glucose infusion rate in diabetic patients with the -786C allele than those without it. In diabetic patients with the -786C allele, plasma nitrate and nitrite concentrations were lower than in subjects without it (p=0.026). No differences were observed between mutant carriers of Glu298Asp and non-carriers among both nondiabetic subjects and Type II diabetic patients. Conclusions/interpretation. The -786T-C mutation of the eNOS gene is associated with insulin resistance in both Japanese non-diabetic subjects and Type II diabetic patients. [Diabetologia (2002[Diabetologia ( ) 45:1594[Diabetologia ( -1601 Keywords Endothelial nitric oxide synthase, polymorphism, glucose infusion rate, homeostasis model assessment of insulin resistance insulin resistance, intima-media thickness. Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita City, Japan a key role in the regulation of vascular tone. Skeletal muscle glucose uptake is enhanced by insulin-mediated vasodilation and the decrease in local blood flow can result in insulin resistance [1][2][3][4][5]. However, several reports deny a major role of endothelial NO production in determining insulin sensitivity [6,7].Recently eNOS knockout mice have been reported to be insulin resistant [8]. These mice have also shown a decrease in whole-body and muscle-glucose uptake as well as the simultaneous decrease in the local blood flow [9]. Two major polymorphisms have been found in the human eNOS gene: Glu298Asp (G894T) in exon 7 and -786T-C mutation in the 5′-flanking region. Glu298Asp causes a structural change of the eNOS Endothelial derived nitric oxide (NO), synthesized from L-arginine by the endothelium isoform of NO synthase (eNOS), mediates local vasodilation and plays

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G894T Polymorphism in the Endothelial Nitric Oxide Synthase Gene Is Associated With an Enhanced Vascular Responsiveness to Phenylephrine

Cited by 168 publications

References 7 publications

Endothelial nitric oxide synthase gene polymorphisms in patients with nontraumatic femoral head osteonecrosis

Endothelial nitric oxide synthase gene polymorphisms in patients with nontraumatic femoral head osteonecrosis

Current Perspectives on Arterial Stiffness and Pulse Pressure in Hypertension and Cardiovascular Diseases

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

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