A Common Variant of the Endothelial Nitric Oxide Synthase (Glu
            <sup>298</sup>
            →Asp) Is a Major Risk Factor for Coronary Artery Disease in the UK

Hingorani, Aroon D.; C, Liang; Fatibene, J; Lyon, Amelia; Monteith, Sue; Parsons, Ann; Haydock, Stephen; Hopper, Ruth; Stephens, Nigel; O’Shaughnessy, Kevin M.; Brown, Morris J.

doi:10.1161/01.cir.100.14.1515

Cited by 491 publications

(396 citation statements)

References 30 publications

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“…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).…”

Section: Ethnicity and Enos Polymorphismssupporting

confidence: 87%

“…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.…”

Section: Ethnicity and Enos Polymorphismsmentioning

confidence: 90%

“…Casas et al; 14 Colombo et al; 15 Yoshimura et al 16 Chang et al; 22 Hingorani et al; 23 Via et al; 24 Wang et al 25 Casas et al 14 Hwang et al; 31 Pulkkinen et al 27 Colombo et al; 15 Rossi et al; 32 Yoshimura et al 16 Casas et al 14 …”

Section: Amiunclassified

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

et al. 2004

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Mutations in the endothelial nitric oxide synthase (eNOS) gene may be associated with abnormal nitric oxide (NO) production and cardiovascular diseases. In this study, we investigated the prevalence of two eNOS polymorphisms, the Glu298Asp variant on exon 7, and the 4a/b variable number of tandem repeats (VNTR) on intron 4, and their association with blood pressure (BP), NO production, salt sensitivity and cardiovascular risk factors in healthy Venezuelans. The prevalence of both polymorphisms in Venezuelans was comparable to that described for Caucasians, but significantly different from that known for African-Americans and Japanese. The 4a/b genotype was associated with reduced levels of NO metabolites (25% decrease), larger BP lowering in response to salt restriction (9.0 vs 4.8 mmHg, Po0.05), greater prevalence of salt sensitivity (39% in 4a/b and 27% in 4b/b; Po0.05) and with higher LDL-cholesterol levels. The Glu298T polymorphism did not affect NO production, nor it was associated with salt sensitivity. Glu298Asp polymorphism was positively associated with higher weight, triglycerides and LDL-cholesterol. Neither polymorphism was associated with changes in fasting or postload serum glucose, BP, obesity and albuminuria. In conclusion, the prevalence of eNOS polymorphisms is strongly determined by ethnic factors. The 4a/b gene polymorphism could be a genetic susceptibility factor for the BP response to salt intake and for the genetic control of NO production. The reduced NO production in subjects with the 4a/b genotype may be responsible for the increased sensitivity of their BP to salt.

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Section: Ethnicity and Enos Polymorphismssupporting

confidence: 87%

Section: Ethnicity and Enos Polymorphismsmentioning

confidence: 90%

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

et al. 2004

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“…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.…”

Section: Discussionmentioning

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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“…It has been demonstrated that this polymorphism is not silent and may possibly be perceived as a target for cleavage (Tesauro et al, 2000). Evidence has been presented that this polymorphism is associated with coronary spasm (Yoshimura et al, 1998), acute myocardial infarction, and coronary artery disease in Caucasians (Hingorani et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

High-Speed Detection of the G894T Polymorphism in Exon 7 of the eNOS Gene by Real-Time Fluorescence PCR with the Light-Cycler

et al. 2004

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A Common Variant of the Endothelial Nitric Oxide Synthase (Glu ²⁹⁸ →Asp) Is a Major Risk Factor for Coronary Artery Disease in the UK

Cited by 491 publications

References 30 publications

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

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

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

High-Speed Detection of the G894T Polymorphism in Exon 7 of the eNOS Gene by Real-Time Fluorescence PCR with the Light-Cycler

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A Common Variant of the Endothelial Nitric Oxide Synthase (Glu 298 →Asp) Is a Major Risk Factor for Coronary Artery Disease in the UK

Cited by 491 publications

References 30 publications

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

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

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

High-Speed Detection of the G894T Polymorphism in Exon 7 of the eNOS Gene by Real-Time Fluorescence PCR with the Light-Cycler

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A Common Variant of the Endothelial Nitric Oxide Synthase (Glu ²⁹⁸ →Asp) Is a Major Risk Factor for Coronary Artery Disease in the UK