title: Endothelial nitric oxide gene polymorphisms and their association with coronary artery disease in Tunisian population.
abstract: OBJECTIVE
  By releasing mediators, like nitric oxide (NO), vascular endothelium is considered so significant in the process of atherosclerotic . In fact, the major functions of NO consist in inhibiting the activation of platelet, relaxing the muscles (vascular and smooth ones), and modulating the growth and the migration of cells (vascular and smooth ones). Therefore, this process makes the endothelial nitric oxide synthase (NOS3) considerably important because it possesses atheroprotective activity. Polymophisms, rs1808593 (10G/T) as well as rs891512 (G24943A) within NOS3 gene, play major role in the coronary artery disease (CAD) development. The aim of the study is to evaluate the relationship between the 10G/T and G24943A polymorphisms and the CAD among Tunisian individuals.
  
  
  METHODS
  We included, in this survey, a set of 274 patients suffering from CAD together with 162 normotensive subjects. The PCR-RFLP was applied to analyze the polymorphism of intron 23 (10G/T) gene, while the ASA-PCR was used to analyze the intronic G24943A gene polymorphism. Overall and subgroup analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association between NOS3 10G/T and G24943A polymorphisms as well as CAD risk. Statistical analysis was performed with SPSS V.10.
  
  
  RESULTS
  The genotype frequencies for G24943A polymorphism differed significantly between the CAD patients and the controls. The former had a frequency of 11.4% for the AA genotype, 34.7% for the GA genotype and 53.9% for the GG genotype. The latter had a frequency of only 2.5% for the AA genotype, 29.7% for the GA genotype and 67.7% for the GG genotype (χ2=7.62; OR=1.79; p=0.006). The CAD patient group showed a significantly-higher frequency of the A allele compared to the controls (0.28 vs. 0.16; χ2=15.20; p<0.001). The odds ratio of CAD for A vs. G allele frequency was statistically significant 1.99 (1.4-2.82) at 95% CI. The genotype distribution for the 3 investigated variants of 10G/T were not significantly different between CAD and control subjects (χ2=1.46; OR=1.72; p=0.22). Whereas, 10G/T has revealed barely allelic (χ2=4.45; OR=2.3; p=0.034) correlation with coronary artery disease Conclusion: The present study was designed so that there would be an association between the CAD and NOS3 polymorphism (G24943A). However, these results have proven that the polymorphism of 10G/T is not associated with CAD in the Tunisian population.
authors.affiliation: Department of Biochemistry, UR12ES07 Research Laboratory, Faculty of Medicine Ibn Jazzar; Sousse-Tunisia. letaief_a@yahoo.fr.
authors.forename: Letaief
authors.initials: L
authors.lastname: Afef
authors.affiliation: Department of Biochemistry, UR12ES07 Research Laboratory, Faculty of Medicine Ibn Jazzar; Sousse-Tunisia.
authors.forename: Benothmane
authors.initials: B
authors.lastname: Leila
authors.affiliation: Department of Biochemistry, UR12ES07 Research Laboratory, Faculty of Medicine Ibn Jazzar; Sousse-Tunisia.
authors.forename: Charfeddine
authors.initials: C
authors.lastname: Bassem
authors.affiliation: Department of Cardiology, Heart Failure (LR12SP09) Research Laboratory, Hospital Farhat Hached; Sousse-Tunisia.
authors.forename: Ernez Hajri
authors.initials: EH
authors.lastname: Samia
authors.affiliation: Department of Cardiology, Heart Failure (LR12SP09) Research Laboratory, Hospital Farhat Hached; Sousse-Tunisia.
authors.forename: Guider
authors.initials: G
authors.lastname: Jridi
authors.affiliation: Department of Biochemistry, UR12ES07 Research Laboratory, Faculty of Medicine Ibn Jazzar; Sousse-Tunisia.
authors.forename: Limem
authors.initials: L
authors.lastname: Khalifa
mesh_terms: D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D014280:Triglycerides / Q000097:blood; D014416:Tunisia
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D002784:Cholesterol; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III