Susceptible and protective eNOS haplotypes in hypertensive black and white subjects

Sandrim, Valéria C.; Coelho, Eduardo Barbosa; Nobre, Fernando; Arado, Gustavo Marin; Lanchote, Vera Lúcia; Tanus‐Santos, José Eduardo

doi:10.1016/j.atherosclerosis.2005.08.003

Cited by 93 publications

(71 citation statements)

References 25 publications

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“…A recent study evaluating the haplotype-based risk of hypertension demonstrated that the haplotype À786C-4b-894G was linked to a protective effect on hypertension risk. 4 Our haplotype results confirmed these findings in Chinese population and supported the potential interaction between TÀ786C and 4a/b variants. Two possible inferences can be drawn here.…”

supporting

confidence: 87%

“…Genetic association studies regarding the relationship between eNOS variants and hypertension, however, have yielded inconsistent results. [4][5][6] Apparent inconsistency generally reflects a lack of statistical power because of a small sample size. To address this issue, we focused on a large Han Chinese population to explore the possible association of the three most widely studied eNOS variants (TÀ786C, 4a/b and G894T), both individually and as haplotypes, with essential hypertension.…”

mentioning

confidence: 99%

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Endothelial nitric oxide synthase genetic variation and essential hypertension risk in Han Chinese: the Fangshan study

et al. 2008

J Hum Hypertens

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confidence: 87%

mentioning

confidence: 99%

Endothelial nitric oxide synthase genetic variation and essential hypertension risk in Han Chinese: the Fangshan study

et al. 2008

J Hum Hypertens

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“…23,24,29,32,51,52 The polymorphism 4a/b was genotyped using electrophoretic differentiation. 1,25,27,28,35,36,[41][42][43][44][45][46][47][48][49] Five studies stated that the controls were age or sex matched. 29,30,38,48,53 24,33 provided data for males and females separately.…”

Section: Eligible Studiesmentioning

confidence: 99%

“…), and disagreements were resolved after a discussion between the 3 authors. Twentyone studies dealt with G894T, 1,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] 16 with 4a/ b, 1,25,27,28,35,36,41-49 7 with T786C, 1,4,29,32,50,51 and 4 with G23T. 24,25,52,53 Seven studies in 4a/b, 1,25,27,28,35,36 4 studies in T786C, 1,29,32 and 2 studies in G23T 24,25 also investigated G894T.…”

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confidence: 99%

Endothelial NO Synthase Gene Polymorphisms and Hypertension

2006

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Abstract-Studies investigated the association between endothelial NO synthase gene polymorphisms and hypertensionreported contradicted or nonconclusive results. A meta-analysis of 35 genetic association studies that examined the relation between hypertension and the G894T, 4a/b, T786C, and G23T polymorphisms of the endothelial nitric oxide synthase gene was carried out. Subgroup analysis by ethnicity and potential sources of heterogeneity and bias were explored. The meta-analysis included genotype data on 7779/10 498, 2216/3222, 2491/3913, and 833/587 cases/controls for G894T, 4b/a, T786C, and G23T, respectively. For the 4b/a polymorphism, overall, the heterogeneity between studies was not significant (Pϭ0.82), and the allele b was associated with a 15% decreased risk of hypertension relative to allele a (odds ratio: 0.85; 95% CI: 0.74 to 0.98). Overall and in whites, the recessive model for allele b produced significant results (odds ratios: 0.78; 95% CI: 0.68 to 0.90 and OR: 0.76 95% CI: 0.62 to 0.92, respectively), whereas the dominant model produced nonsignificant results. In studies involved East Asians and blacks, an association was not demonstrated.Regarding the G894T, T768C, and G23T polymorphisms, in no case (ie, overall, in whites, or in East Asians) was a statistically significant association and heterogeneity found. There was no substantial source of bias in the selected studies. In conclusion, there is evidence of association only between 4b/a polymorphism and hypertension; however, studies exploring combinations of the polymorphisms may help us better understand the genetics of hypertension. Key Words: nitric oxide Ⅲ polymorphism Ⅲ meta-analysis H ypertension is a multifactorial disease involving both environmental and genetic components. 1 Clinical and animal studies have suggested that an alteration in NO metabolism may be a contributing factor in the pathogenesis of hypertension. [2][3][4] Thus, abnormalities in the activity of the enzyme endothelial NO synthase (eNOS) that synthesize NO in endothelial cells may lead to NO deficiency. The gene encoding eNOS is located on chromosome 7 (7q35-q36) and contains 26 exons with an entire length of 21kb. G894T (Glu298Asp in exon 7), intron 4 (4b/a), (T-786)C (T786C), and G23T are the most clinically relevant polymorphisms in the eNOS gene that have been described. 5 The genetic association studies that examined whether the polymorphisms in the eNOS gene are associated with hypertension have provided controversial or inconclusive results, partly because each study involved few cases and few controls and, therefore, there was not enough information to demonstrate association. Furthermore, the interpretation is complicated by the fact that different populations, sampling strategies, genotyping procedures, and number of loci included in the analyses have been used. To shed some light on these contradictory results, as well as to decrease the uncertainty of the effect size of estimated risk, a meta-analysis 6 of all of the available studies related the G894T...

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“…15 Importantly, studies have found associations between polymorphisms or haplotypes of the eNOS gene and hypertension in black and white subjects, in patients with type 2 diabetes mellitus and in pregnant women. [16][17][18][19][20] However, very few studies took into consideration the possible interaction of eNOS polymorphisms and obesity, 21 and no previous work has studied these polymorphisms in obese children and adolescents with or without hypertension. This interaction may be very relevant because obesity may interact with eNOS polymorphisms and affect NO formation.…”

Section: Introductionmentioning

confidence: 99%

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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Susceptible and protective eNOS haplotypes in hypertensive black and white subjects

Cited by 93 publications

References 25 publications

Endothelial nitric oxide synthase genetic variation and essential hypertension risk in Han Chinese: the Fangshan study

Endothelial nitric oxide synthase genetic variation and essential hypertension risk in Han Chinese: the Fangshan study

Endothelial NO Synthase Gene Polymorphisms and Hypertension

eNOS haplotype associated with hypertension in obese children and adolescents

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