eNOS haplotype associated with hypertension in obese children and adolescents

Abstract

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.

The effects of endothelial nitric oxide synthase tagSNPs on nitrite levels and risk of hypertension and obesity in children and adolescents

“…10,11 Clinically relevant polymorphisms and their combinations within haplotypes affect both the susceptibility to hypertension and nitrite levels. [13][14][15][16][17] However, tagSNPs provide further NOS3 genetic variation, which has been previously investigated. 42,43 In fact, haplotypes including the tagSNPs rs3918226 and rs743506 were associated with other conditions involving cardiovascular alterations.…”

“…10,11 Conversely, reduced NO formation is associated with hypertension, 12 and single-nucleotide polymorphisms (SNPs) of NOS3 gene were associated with hypertension, particularly combinations of three clinically relevant polymorphisms in the NOS3 gene: the SNPs rs2070744 in the promoter region, rs1799983 in exon 7, and a 27-bp variable number of tandem repeats in intron 4. [13][14][15][16][17] More recently, other tagSNPs in the NOS3 gene, which represent the information of neighboring SNPs in linkage disequilibrium (rs3918188, rs743506 and rs7830), were associated with alterations in the vascular function and low levels of NO in adults. [18][19][20] Importantly, one (rs3918226) of these tagSNPs was recently associated with hypertension in two large genome-wide association studies, 21,22 although it apparently does not affect NO formation in healthy subjects.…”

A NOS3 Polymorphism Determines Endothelial Response to Folate in Children with Type 1 Diabetes or Obesity

“…24 NOS3 polymorphisms have previously been associated with obesity and hypertension in adolescents. 37 Although our numbers are too small to accurately determine whether NOS3 polymorphisms may be risk alleles for obesity in childhood, this data together suggests further evaluation of genetic variation in NOS3 and obesity risk in childhood is warranted.…”

Endothelial Nitric Oxide Synthase G894T Gene Polymorphism and Essential Hypertension in the Chinese Population: a Meta-Analysis Involving 11,248 Subjects

“…In 2010, Souza-Costa et al found that the eNOS haplotype, Glu of Glu298Asp was associated with hypertension in obese children and adolescents of Brazil (40). 3) Other factors, such as the research methods, the statistical methods and the sample size.…”