RGD Reference Report - Endothelial nitric oxide synthase gene intron 4 VNTR polymorphism in sickle cell disease: relation to vasculopathy and disease severity. - Rat Genome Database

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Endothelial nitric oxide synthase gene intron 4 VNTR polymorphism in sickle cell disease: relation to vasculopathy and disease severity.

Authors: Tantawy, AA  Adly, AA  Ismail, EA  Aly, SH 
Citation: Tantawy AA, etal., Pediatr Blood Cancer. 2015 Mar;62(3):389-94. doi: 10.1002/pbc.25234. Epub 2014 Sep 27.
RGD ID: 11533931
Pubmed: (View Article at PubMed) PMID:25263931
DOI: Full-text: DOI:10.1002/pbc.25234

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. PROCEDURE: 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.



Disease Annotations    
acute chest syndrome  (IAGP,ISO)
Stroke  (IAGP,ISO)
Vaso-occlusive Crisis  (IAGP,ISO)

Phenotype Annotations    

Human Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Nos3  (nitric oxide synthase 3)

Genes (Mus musculus)
Nos3  (nitric oxide synthase 3, endothelial cell)

Genes (Homo sapiens)
NOS3  (nitric oxide synthase 3)


Additional Information