title: Endothelial nitric oxide synthase gene intron 4 VNTR polymorphism in sickle cell disease: relation to vasculopathy and disease severity.
abstract: BACKGROUND
  Impaired NO bioavailability represents the central feature of endothelial dysfunction, and is a common denominator in the pathogenesis of vasculopathy in sickle cell disease (SCD). Evidence indicates the contribution of 4a allele of endothelial NO synthase (eNOS) gene to cardiac and renal diseases. We studied the 27-base pair tandem repeat polymorphism in intron 4 of eNOS gene in 51 patients with SCD compared with 55 healthy controls and evaluated its role in disease severity and hemolysis-associated complications.
  
  
  METHODS
  Transfusion history, vaso-occlusive crisis, thrombotic events, urinary albumin excretion, and echocardiography were assessed. Analysis of eNOS intron 4 gene polymorphism was performed by polymerase chain reaction.
  
  
  RESULTS
  The distribution of eNOS alleles and genotypes was similar between patients with SCD and controls. Compared with bb genotype, the frequency of eNOS4a allele (aa and ab genotypes) was significantly higher in patients with elevated tricuspid regurgitant velocity (TRV) (P = 0.009), nephropathy (P = 0.006), or history of cerebral stroke (P = 0.029). Logistic regression analysis revealed that eNOS4a allele was an independent risk factor for elevated TRV (P < 0.001). Patients with SCD and eNOS4a allele had higher lactate dehydrogenase, serum ferritin, D-Dimer, and von Willebrand factor antigen (P < 0.05).
  
  
  CONCLUSIONS
  We suggest that eNOS intron 4 gene polymorphism is related to endothelial dysfunction and vasculopathy in SCD and could provide utility for prediction of increased susceptibility to vascular complications.
authors.affiliation: Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Azza Abdel Gawad
authors.initials: AA
authors.lastname: Tantawy
authors.forename: Amira Abdel Moneam
authors.initials: AA
authors.lastname: Adly
authors.forename: Eman Abdel Rahman
authors.initials: EA
authors.lastname: Ismail
authors.forename: Shereen Hussiny
authors.initials: SH
authors.lastname: Aly
mesh_terms: D000293:Adolescent; D000483:Alleles; D000755:Anemia, Sickle Cell / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000201:enzymology; D005260:Female; D005293:Ferritins / Q000097:blood; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005787:Gene Frequency; D006801:Humans; D006836:Hydro-Lyases / Q000097:blood; D007438:Introns; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D020521:Stroke / Q000201:enzymology / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D020080:Tandem Repeat Sequences; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C029417:Von Willebrand antigen; C036309:fibrin fragment D; D014841:von Willebrand Factor; D005293:Ferritins; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D006836:Hydro-Lyases; C045581:lactate dehydratase
keywords: SCD; endothelial dysfunction; nitric oxide synthase gene polymorphism