Evidence of Association of the ecNOS Gene Polymorphism with Plasma NO Metabolite Levels in Humans

Tsukada, Toshihiko; Yokoyama, Keitaro; Arai, Tomoko; Takemoto, Fumi; Hara, Sigeko; Yamada, Akira; Kawaguchi, Yoshindo; Hosoya, Tatsuo; Igari, J

doi:10.1006/bbrc.1998.8267

Cited by 406 publications

(295 citation statements)

References 13 publications

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“…The a allele was found more frequently in African-Americans (27-31%) than in Caucasians (16-18%) or Japanese (10-13%). 9,26,[34][35][36][37] Once again the frequency of a allele in Venezuelan subjects most closely compared to that of the Caucasians, since it was found in 18% of the Venezuelan subjects studied.…”

Section: Ethnicity and Enos Polymorphismsmentioning

confidence: 85%

“…Decreases in plasma NO metabolites have also been reported in healthy Japanese carrying the 4a/b genotype. 37 Owing to the existing relationship between reduced NO levels and salt sensitivity (see above), we propose that the reduced production of NO observed in subjects harbouring the 4a/b genotype could be responsible for the greater sensitivity of their BP to dietary salt. In addition to salt sensitivity, the 4a/b polymorphism has been shown to determine the efficacy of nevibolol, a betablocker that in addition increases the production of NO.…”

Section: Ethnicity and Enos Polymorphismsmentioning

confidence: 91%

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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 Polymorphismsmentioning

confidence: 85%

Section: Ethnicity and Enos Polymorphismsmentioning

confidence: 91%

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

et al. 2004

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“…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%

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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“…A larger 4b allele contains five repeats of the 27-bp fragment, whereas the smaller one contains only four and is associated with a lower level of NO metabolites. 12,13 As NO seems to have multiple atheroprotective effects, we hypothesized that the eNOS Glu298Asp polymorphism may be a risk factor for susceptibility to cardiovascular alterations. In the present study of families, selected at random in the general population, we analysed the relationship between polymorphisms of the eNOS gene (in exon 7 and intron 4) and ambulatory blood pressure (ABP), left ventricular mass (LVM), intimamedia thickness (IMT) and pulse wave velocity (PWV).…”

Section: Introductionmentioning

confidence: 99%

Ambulatory blood pressure, left ventricular mass and vascular phenotypes in relation to the endothelial nitric oxide synthase gene Glu298Asp and intron 4 polymorphisms in a population-based family study

et al. 2005

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Reduced nitric oxide production is associated with pathological changes in the cardiovascular system. In a study of randomly chosen families, we analysed the relationship between two polymorphisms (Glu298Asp and intron 4) of the endothelial nitric oxide synthase (eNOS) and ambulatory blood pressure (ABP), left ventricular mass index (LVMI) and vascular phenotypes. The study population consisted of 127 parents and 167 offspring. All subjects underwent 24 h ABP monitoring using a SpaceLabs 90207 device. 2D and M-mode echocardiograms were obtained. Pulse wave velocity between the common carotid and femoral artery was measured with the Complior s device, and the carotid intima-media thickness (IMT) was assessed by ultrasound. For statistical analysis, covariables and correlations between relatives were taken into account. The frequency of genotypes was as follows: for Glu298Asp:55.1%-Glu/Glu, 40.1%-Glu/Asp and 4.8%-Asp/Asp; for intron 4: 65.0%-4 b/b, 33.3%-4 b/a and 1.7%-4 a/a, being in Hardy-Weinberg equilibrium (PX0.29). There was no relationship between the eNOS gene polymorphisms and ABP or LVMI either in parents or their offspring. Among parents, carriers of the 298Asp allele had higher IMT values as compared with Glu/Glu homozygotes (0.94 vs 0.70 mm; P ¼ 0.007). Among offspring, there was a similar tendency (0.60 vs 0.53 mm; P ¼ 0.10), which was confirmed by transmission disequilibrium tests for quantitative variables (PX0.07). Our findings indicate that the Glu298Asp polymorphism of eNOS identifies patients with larger carotid IMT, also in younger subjects.

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Evidence of Association of the ecNOS Gene Polymorphism with Plasma NO Metabolite Levels in Humans

Cited by 406 publications

References 13 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

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

Ambulatory blood pressure, left ventricular mass and vascular phenotypes in relation to the endothelial nitric oxide synthase gene Glu298Asp and intron 4 polymorphisms in a population-based family study

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