eNOS gene T-786C polymorphism modulates atorvastatin-induced increase in blood nitrite

Nagassaki, Sabrina; Sertório, Jonas T.; Metzger, Ingrid F.; Andreza, F.; Rocha, João Batista Teixeira da; Tanus‐Santos, José Eduardo

doi:10.1016/j.freeradbiomed.2006.04.026

Cited by 73 publications

(52 citation statements)

References 43 publications

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“…Furthermore, eNOS gene polymorphism does not influence the oxidative stress status under basal conditions. Our data agree with a previous study that showed that eNOS gene polymorphism at position -786T>C had no influence on the MDA levels of young subjects (31).…”

Section: Discussionsupporting

confidence: 93%

Influence of eNOS gene polymorphism on cardiometabolic parameters in response to physical training in postmenopausal women

Sponton

Malagrino

Carvalho

et al. 2011

Braz J Med Biol Res

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The health-promoting effects of exercise training (ET) are related to nitric oxide (NO) production and/or its bioavailability. The objective of this study was to determine whether single nucleotide polymorphism of the endothelial NO synthase (eNOS) gene at positions -786T>C, G894T (Glu298Asp) and at the variable number of tandem repeat (VNTR) Intron 4b/a would interfere with the cardiometabolic responses of postmenopausal women submitted to physical training. Forty-nine postmenopausal women were trained in sessions of 30-40 min, 3 days a week for 8 weeks. Genotypes, oxidative stress status and cardiometabolic parameters were then evaluated in a double-blind design. Both systolic and diastolic blood pressure values were significantly reduced after ET, which was genotype-independent. However, women without eNOS gene polymorphism at position -786T>C (TT genotype) and Intron 4b/a (bb genotype) presented a better reduction of total cholesterol levels (-786T>C: before = 213 ± 12.1, after = 159.8 ± 14.4, Δ = -24.9% and Intron 4b/a: before = 211.8 ± 7.4, after = 180.12 ± 6.4 mg/dL, Δ = -15%), and LDL cholesterol (-786T>C: before = 146.1 ± 13.3, after = 82.8 ± 9.2, Δ = -43.3% and Intron 4b/a: before = 143.2 ± 8, after = 102.7 ± 5.8 mg/dL, Δ = -28.3%) in response to ET compared to those who carried the mutant allele. Superoxide dismutase activity was significantly increased in trained women whereas no changes were observed in malondialdehyde levels. Women without eNOS gene polymorphism at position -786T>C and Intron 4b/a showed a greater reduction of plasma cholesterol levels in response to ET. Furthermore, no genotype influence was observed on arterial blood pressure or oxidative stress status in this population.

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Section: Discussionsupporting

confidence: 93%

Influence of eNOS gene polymorphism on cardiometabolic parameters in response to physical training in postmenopausal women

Sponton

Malagrino

Carvalho

et al. 2011

Braz J Med Biol Res

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“…16,26 Although no earlier study has examined whether eNOS polymorphisms or haplotypes modify the effects of drugs used to treat GH or PE, a few studies showed that eNOS polymorphisms affect the responses to drugs that upregulate eNOS expression or increased NO release. [27][28][29][30][31] In this study, we found that eNOS polymorphisms do not affect responses to methyldopa, which was used in as an initial therapy for hypertensive disorders of pregnancy. Although there is no evidence that methyldopa produces antihypertensive effects by mechanisms involving increased NO production, it has been reported that several calcium channel blockers (including nifedipine) may improve endothelial function and restore NO bioavailability.…”

Section: Discussionmentioning

confidence: 66%

eNOS haplotypes affect the responsiveness to antihypertensive therapy in preeclampsia but not in gestational hypertension

et al. 2009

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Variations of the endothelial nitric oxide synthase (eNOS) gene have been associated with hypertensive disorders of pregnancy. We examined whether eNOS polymorphisms affect the therapeutic responses of women with gestational hypertension (GH) or preeclampsia (PE). We studied 304 hypertensive pregnant women (152 GH and 152 PE), who were stratified according to clinical and laboratorial parameters of therapeutic responsiveness. We compared the frequencies of three eNOS genetic polymorphisms (T-786C, Glu298Asp and b/a intron 4) in responsive and nonresponsive PE and GH patients. We found no significant differences in genotype or allele distributions when responsive and nonresponsive groups were compared (both PE or GH; all P40.05). However, the eNOS haplotype distribution differed in PE (but not in GH)-responsive and -nonresponsive groups (P ¼ 0.0003). The 'C-Glu-a' and 'T-Asp-a' hapotypes were associated with responsiveness and nonresponsiveness to therapy, respectively (both Po0.001), thus suggesting that eNOS haplotypes affect the responsiveness to antihypertensive therapy in PE.

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“…12 Briefly, this solution contains 0.8 M ferricyanide and 1% NP-40. The samples were analyzed for their nitrite content using an ozone-based chemiluminescence assay, as previously described.…”

Section: Subjectsmentioning

confidence: 99%

“…7,8 Indeed, endothelium-derived NO has a major role in vascular homeostasis, causes vasodilation, prevents platelet and leukocyte adhesion, and inhibits vascular smooth muscle cell migration and proliferation. 9 Recent studies have shown that polymorphisms in the gene encoding endothelial nitric oxide synthase (eNOS), the most important enzyme that synthesizes NO in the endothelial cells, affect NO formation, 10,11 drug responses, [12][13][14] and are associated with cardiovascular diseases. 15 Three clinically relevant polymorphisms in this gene have been widely studied: a single-nucleotide polymorphism (SNP) in the promoter region (T À786 C, rs 2070744), an SNP in exon 7 (G894T, rs 1799983) and the variable number of tandem repeats (VNTRs) in intron 4.…”

Section: Introductionmentioning

confidence: 99%

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eNOS haplotype associated with hypertension in obese children and adolescents

et al. 2010

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Objective: The aim of our study is to investigate whether genetic polymorphisms in the endothelial nitric oxide synthase (eNOS) gene (in the promoter region T À786 C, in exon 7 (Glu298Asp) and in intron 4 (4b/4a)) or eNOS haplotypes are associated with hypertension in obese children and adolescents. Methods: We genotyped 175 healthy (controls), 110 normotensive obese and 73 hypertensive obese children and adolescents. Genotypes were determined by Taqman allele discrimination assay and real-time PCR, and by PCR followed by fragment separation by electrophoresis. We compared the distribution of eNOS genotypes, alleles and haplotypes in the three study groups of subjects. We have also measured whole-blood nitrite concentrations. Results: The 4a4a genotype for the intron 4 polymorphism was more common in normotensive obese and hypertensive obese (Po0.01). The AspAsp genotype for Glu298Asp polymorphism was less common in normotensive obese (Po0.02). No significant differences were found in allele distributions for the three eNOS polymorphisms. However, the haplotype combining the C, 4b and Glu variants for the three polymorphisms was more common in hypertensive obese than in normotensive obese or control children and adolescents (odds ratio ¼ 2.28 and 2.79, respectively; 95% confidence interval: 1.31-4.31 and 1.39-5.64, respectively; both Po0.00625). This haplotype was not associated with significantly different nitrite concentrations (P40.05). Conclusions: Our findings suggest that the eNOS haplotype, C b Glu, is associated with hypertension in obese children and adolescents. Further studies examining the possible interactions of eNOS haplotypes with environmental factors and other genetic markers involved in the development of obesity and its complications are warranted.

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eNOS gene T-786C polymorphism modulates atorvastatin-induced increase in blood nitrite

Cited by 73 publications

References 43 publications

Influence of eNOS gene polymorphism on cardiometabolic parameters in response to physical training in postmenopausal women

Influence of eNOS gene polymorphism on cardiometabolic parameters in response to physical training in postmenopausal women

eNOS haplotypes affect the responsiveness to antihypertensive therapy in preeclampsia but not in gestational hypertension

eNOS haplotype associated with hypertension in obese children and adolescents

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