title: 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(-786)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 (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.
authors.affiliation: Department of Biology, Federal University of Juiz de Fora, Minas Gerais, Brazil.
authors.forename: D C
authors.initials: DC
authors.lastname: Souza-Costa
authors.forename: V A
authors.initials: VA
authors.lastname: Belo
authors.forename: P S
authors.initials: PS
authors.lastname: Silva
authors.forename: Jonas T
authors.initials: JT
authors.lastname: Sertorio
authors.forename: I F
authors.initials: IF
authors.lastname: Metzger
authors.forename: C M
authors.initials: CM
authors.lastname: Lanna
authors.forename: M A
authors.initials: MA
authors.lastname: Machado
authors.forename: J E
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D000293:Adolescent; D002648:Child; D004586:Electrophoresis; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000235:genetics*; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000097:blood / Q000235:genetics*; D009765:Obesity / Q000097:blood / Q000150:complications / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D052250:Nitric Oxide Synthase Type III