title: Functional G894T (rs1799983) polymorphism and intron-4 VNTR variant of nitric oxide synthase (NOS3) gene are susceptibility biomarkers of obesity among Tunisians.
abstract: The endothelial nitric oxide synthase (NOS3) has been shown to play a role in the modulation of lipolysis. The goal of this study was to examine the impact of the G894T (rs1799983) and a 27 bp variable number of tandem repeats (VNTR 4a/b) of NOS3 gene on obesity in a sample of the Tunisian population.
  
  
  
  The study included 211 normal weight subjects and 183 obese patients. NOS3 G894T and 4a/b variants were determined by PCR analysis and examined for association with obesity-related traits. The effect of obesity on forearm skin blood flow (FSBF) response to acetylcholine, an endothelium-dependent vasodilator was determined by laser Doppler iontophoresis.
  
  
  
  In case-control studies, both G894T and 4a/b variants were associated with obesity. A significantly increased risk of obesity was found with the NOS3(G894T) TT genotype (OR:2.62, P=0.04). This association remains significant after adjustments for age and gender (OR: 2.93, P=0.03). A higher risk was also observed for carriers of the G894T allele (OR: 1.72, P=0.001). Stratified analysis by gender revealed that obese men (but not women) had significantly higher frequency of TT genotypes compared to controls (9.9% vs. 2.9%, P=0.01). Carriers of the 4b allele presented a significantly higher risk of obesity than non-carriers even after adjustments for age and gender (OR (95%CI): 1.72 (1.16-2.56), P=0.004). Correlations with anthropometric parameters revealed that carriers of TT and bb genotypes had significantly higher body mass index compared to those homozygous for the G and a alleles (P=0.0004).
  
  
  
  This study provides the first evidence for the association of G894T and 4a/b variants with body mass index and the risk of obesity in Tunisians. These polymorphisms did not exhibit, however any significant association with both metabolic traits and vascular function.
authors.affiliation: Unité de Recherche UR12ESO6, Physiologie de l'Exercice et Physiopathologie: de l'Intégré au Moléculaire «Biologie, Medecine et Santé», Faculté de Medecine Ibn el Jazzar, Sousse, Tunisia.
authors.forename: Hela Ben
authors.initials: HB
authors.lastname: Nasr
authors.affiliation: Unité de Recherche UR12ESO6, Physiologie de l'Exercice et Physiopathologie: de l'Intégré au Moléculaire «Biologie, Medecine et Santé», Faculté de Medecine Ibn el Jazzar, Sousse, Tunisia.
authors.forename: Saloua
authors.initials: S
authors.lastname: Dimassi
authors.affiliation: Unité de Recherche UR12ESO6, Physiologie de l'Exercice et Physiopathologie: de l'Intégré au Moléculaire «Biologie, Medecine et Santé», Faculté de Medecine Ibn el Jazzar, Sousse, Tunisia.
authors.forename: Refka
authors.initials: R
authors.lastname: M'hadhbi
authors.affiliation: Unité de Recherche UR12ESO6, Physiologie de l'Exercice et Physiopathologie: de l'Intégré au Moléculaire «Biologie, Medecine et Santé», Faculté de Medecine Ibn el Jazzar, Sousse, Tunisia.
authors.forename: Haithem
authors.initials: H
authors.lastname: Debbabi
authors.affiliation: Laboratoire d'Hématologie, CHU Farhat Hached, Sousse, Tunisia.
authors.forename: Mondher
authors.initials: M
authors.lastname: Kortas
authors.affiliation: Unité de Recherche UR12ESO6, Physiologie de l'Exercice et Physiopathologie: de l'Intégré au Moléculaire «Biologie, Medecine et Santé», Faculté de Medecine Ibn el Jazzar, Sousse, Tunisia.
authors.forename: Zouhair
authors.initials: Z
authors.lastname: Tabka
authors.affiliation: Unité de Recherche UR12ESO6, Physiologie de l'Exercice et Physiopathologie: de l'Intégré au Moléculaire «Biologie, Medecine et Santé», Faculté de Medecine Ibn el Jazzar, Sousse, Tunisia; Département de Biologie, Faculté des Sciences de Sfax, Tunisia. Electronic address: k.chahed@yahoo.fr.
authors.forename: Karim
authors.initials: K
authors.lastname: Chahed
mesh_terms: D000328:Adult; D000483:Alleles; D015992:Body Mass Index; D016022:Case-Control Studies; D004198:Disease Susceptibility; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014416:Tunisia
chemical_list: D005819:Genetic Markers; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: Body mass index; G894T polymorphism; NOS3; Obesity; VNTR 4a/b variant