{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T21:12:35Z","timestamp":1775164355857,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,9,27]],"date-time":"2014-09-27T00:00:00Z","timestamp":1411776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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 (<jats:italic>eNOS<\/jats:italic>) gene to cardiac and renal diseases. We studied the 27\u2010base pair tandem repeat polymorphism in intron 4 of<jats:italic>eNOS<\/jats:italic>gene in 51 patients with SCD compared with 55 healthy controls and evaluated its role in disease severity and hemolysis\u2010associated complications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>Transfusion history, vaso\u2010occlusive crisis, thrombotic events, urinary albumin excretion, and echocardiography were assessed. Analysis of<jats:italic>eNOS<\/jats:italic>intron 4 gene polymorphism was performed by polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The distribution of<jats:italic>eNOS<\/jats:italic>alleles and genotypes was similar between patients with SCD and controls. Compared with bb genotype, the frequency of<jats:italic>eNOS4a<\/jats:italic>allele (aa and ab genotypes) was significantly higher in patients with elevated tricuspid regurgitant velocity (TRV) (<jats:italic>P<\/jats:italic>\u2009=\u20090.009), nephropathy (<jats:italic>P<\/jats:italic>\u2009=\u20090.006), or history of cerebral stroke (<jats:italic>P<\/jats:italic>\u2009=\u20090.029). Logistic regression analysis revealed that<jats:italic>eNOS4a<\/jats:italic>allele was an independent risk factor for elevated TRV (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). Patients with SCD and<jats:italic>eNOS4a<\/jats:italic>allele had higher lactate dehydrogenase, serum ferritin, D\u2010Dimer, and von Willebrand factor antigen (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We suggest that<jats:italic>eNOS<\/jats:italic>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. Pediatr Blood Cancer 2015;62:389\u2013394. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.25234","type":"journal-article","created":{"date-parts":[[2014,9,28]],"date-time":"2014-09-28T02:20:01Z","timestamp":1411870801000},"page":"389-394","source":"Crossref","is-referenced-by-count":19,"title":["Endothelial nitric oxide synthase gene intron 4 VNTR polymorphism in sickle cell disease: Relation to vasculopathy and disease severity"],"prefix":"10.1002","volume":"62","author":[{"given":"Azza Abdel Gawad","family":"Tantawy","sequence":"first","affiliation":[{"name":"Pediatrics Department Faculty of Medicine Ain Shams University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amira Abdel Moneam","family":"Adly","sequence":"additional","affiliation":[{"name":"Pediatrics Department Faculty of Medicine Ain Shams University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eman Abdel Rahman","family":"Ismail","sequence":"additional","affiliation":[{"name":"Clinical Pathology Department Faculty of Medicine Ain Shams University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shereen Hussiny","family":"Aly","sequence":"additional","affiliation":[{"name":"Pediatrics Department Faculty of Medicine Ain Shams University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,9,27]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2008.1.177"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.293.13.1653"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2005.1.51"},{"key":"e_1_2_5_5_1","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0031-6997(25)06663-3","article-title":"Nitric oxide: Physiology, pathophysiology, and pharmacology","volume":"43","author":"Moncada S","year":"1991","journal-title":"Pharmacol Rev"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90267-4"},{"key":"e_1_2_5_7_1","first-page":"F561","article-title":"Biosynthesis and homeostatic roles of nitric oxide in the normal kidney","volume":"272","author":"Kone BC","year":"1997","journal-title":"Am J Physiol"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.1146"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(01)00327-3"},{"key":"e_1_2_5_10_1","first-page":"683","article-title":"Endothelial nitric oxide synthase gene intron4 VNTR polymorphism in patients with coronary artery disease in Iran","volume":"124","author":"Salimi S","year":"2006","journal-title":"Indian J Med Res"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/MBC.0b013e328346ef71"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/14.12.2898"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.32.1.3"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.32.3.521"},{"key":"e_1_2_5_15_1","first-page":"2432","article-title":"A new electrophoresis technique to separate microsatellite alleles","volume":"8","author":"Wang X","year":"2009","journal-title":"J Biotechnol"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.2353\/jmoldx.2009.080173"},{"key":"e_1_2_5_17_1","first-page":"1013","article-title":"Sickle cell disease in childhood: Part I. 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