eNOS haplotype associated with hypertension in obese children and adolescents

• Published in: International Journal of Obesity Vol. 35; no. 3; pp. 387 - 392
• Main Authors: Souza-Costa, D.C, Belo, V.A, Silva, P.S, Metzger, I.F, Lanna, C.M, Machado, M.A, Tanus-Santos, J.E
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.03.2011; Nature Publishing Group UK
• Subjects: 631/208/726/649; 631/208/728; 631/443/1338/243; 692/699/2743/393; Adolescent; Adolescents; alleles; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood; Blood and lymphatic vessels; Body mass index; Cardiology. Vascular system; Child; Children; complications; Complications and side effects; confidence interval; Diabetes; Electrophoresis; Endocrinology; endothelial nitric oxide synthase; Environmental factors; Epidemiology; exons; Female; General aspects; Genetic aspects; Genetic markers; genetic polymorphism; genetics; Genotype; Genotypes; Haplotypes; Haplotypes - genetics; Health Promotion and Disease Prevention; Humans; Hypertension; Hypertension - blood; Hypertension - complications; Hypertension - genetics; Internal Medicine; introns; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Nitric oxide; Nitric Oxide Synthase Type III; Nitric Oxide Synthase Type III - blood; Nitric Oxide Synthase Type III - genetics; Obesity; Obesity - blood; Obesity - complications; Obesity - genetics; Obesity in children; original-article; Pharmacology; Physiological aspects; Polymorphism; Polymorphism, Genetic; Polymorphism, Genetic - genetics; promoter regions; Public Health; quantitative polymerase chain reaction; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors; Teenagers; Brazil; eNOS; nitric oxide; haplotypes; children; hypertension; Human; Hypertension; Obesity; Nutrition; Nutrition disorder; Cardiovascular disease; Metabolic diseases; Association; Nitric oxide; Adolescent; Child; Haplotype; Nutritional status
• ISSN: 0307-0565; 1476-5497; 1476-5497
• DOI: 10.1038/ijo.2010.146

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−786C, 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 (P<0.01). The AspAsp genotype for Glu298Asp polymorphism was less common in normotensive obese (P<0.02). 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=2.28 and 2.79, respectively; 95% confidence interval: 1.31–4.31 and 1.39–5.64, respectively; both P<0.00625). This haplotype was not associated with significantly different nitrite concentrations (P>0.05). 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.