title: Endothelial nitric oxide synthase gene intron 4 variable number tandem repeat polymorphism in β-thalassemia major: relation to cardiovascular complications.
abstract: Endothelial nitric oxide synthase (eNOS), an enzyme that generates nitric oxide, is a major determinant of endothelial function. Several eNOS gene polymorphisms have been reported as 'susceptibility genes' in various human diseases states, including cardiovascular, pulmonary and renal diseases. We studied the 27-base pair tandem repeat polymorphism in intron 4 of eNOS gene in 60 β-thalassemia major (β-TM) patients compared with 60 healthy controls and assessed its role in subclinical atherosclerosis and vascular complications. Patients were evaluated stressing on transfusion history, splenectomy, thrombotic events, echocardiography and carotid intima-media thickness (CIMT). Analysis of eNOS intron 4 gene polymorphism was performed by PCR. No significant difference was found between β-TM patients and controls with regard to the distribution of eNOS4 alleles or genotypes. The frequency of eNOS4a allele (aa and ab genotypes) was significantly higher in β-TM patients with pulmonary hypertension or cardiomyopathy. Logistic regression analysis revealed that eNOS4a allele was an independent risk factor for pulmonary hypertension in β-TM patients [odds ratio (OR) 2.2, 95% confidence interval (95% CI) 1.19-5.6; P < 0.001]. We suggest that eNOS intron 4 gene polymorphism is related to endothelial dysfunction and subclinical atherosclerosis and could be a possible genetic marker for prediction of increased susceptibility to cardiovascular complications.
authors.affiliation: aDepartment of Pediatrics bDepartment of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Azza A G
authors.initials: AA
authors.lastname: Tantawy
authors.forename: Amira A M
authors.initials: AA
authors.lastname: Adly
authors.forename: Eman A
authors.initials: EA
authors.lastname: Ismail
authors.forename: Shereen H
authors.initials: SH
authors.lastname: Aly
mesh_terms: D000293:Adolescent; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000235:genetics*; D059168:Carotid Intima-Media Thickness; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007438:Introns; D008297:Male; D018598:Minisatellite Repeats; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D017086:beta-Thalassemia / Q000150:complications* / Q000235:genetics*
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III