{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T13:26:16Z","timestamp":1791033976174,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,8,30]],"date-time":"2012-08-30T00:00:00Z","timestamp":1346284800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The association of vascular endothelial growth factor (<jats:italic><jats:styled-content style=\"fixed-case\">VEGFA<\/jats:styled-content><\/jats:italic>) variants and <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> secretion with sickle cell disease (<jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>) vasoocclusive crisis (<jats:styled-content style=\"fixed-case\">VOC<\/jats:styled-content>) was investigated in 210 <jats:styled-content style=\"fixed-case\">VOC<\/jats:styled-content> patients and 114 pain\u2010free control patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic><jats:styled-content style=\"fixed-case\">VEGFA<\/jats:styled-content><\/jats:italic> \u22122578<jats:styled-content style=\"fixed-case\">C\/A<\/jats:styled-content> (rs699947), \u2212460<jats:styled-content style=\"fixed-case\">T\/C<\/jats:styled-content> (rs833061), \u22121154<jats:styled-content style=\"fixed-case\">G\/A<\/jats:styled-content> (rs15703060), \u2212634<jats:styled-content style=\"fixed-case\">G\/C<\/jats:styled-content> (rs2010963), 398<jats:styled-content style=\"fixed-case\">G\/A<\/jats:styled-content> (rs833068), 497<jats:styled-content style=\"fixed-case\">G\/A<\/jats:styled-content> (rs833070), \u2212583<jats:styled-content style=\"fixed-case\">T\/C<\/jats:styled-content> (rs3025020), and 936<jats:styled-content style=\"fixed-case\">C\/T<\/jats:styled-content> (rs3025039) were carried out by real\u2010time <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Higher frequency of rs2010963 <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\u2010allele, rs833068 <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\u2010allele, and rs3025020 <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\u2010allele and significant differences in rs2010963, rs833068, and rs3025020 genotype distribution were seen in <jats:styled-content style=\"fixed-case\">VOC<\/jats:styled-content> than steady\u2010state patients. Increased <jats:styled-content style=\"fixed-case\">VOC<\/jats:styled-content> risk was seen with rs2010963 as heterozygous and more as homozygous, and in rs833068 and rs3025020 homozygous carriers. While there were no differences in <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> levels between <jats:styled-content style=\"fixed-case\">VOC<\/jats:styled-content> and steady\u2010state controls, there was a progressive decline in serum <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> in rs2010963 and rs833068 heterozygous and homozygous genotypes, but an opposite trend was seen in <jats:styled-content style=\"fixed-case\">VOC<\/jats:styled-content> patients. Haploview analysis revealed high <jats:styled-content style=\"fixed-case\">LD<\/jats:styled-content> between rs699947, rs833061, rs1570360, rs2010963, rs833068, and rs833070, but weak or no <jats:styled-content style=\"fixed-case\">LD<\/jats:styled-content> between rs3025020 and rs3025039 and other <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s. Six\u2010locus (rs699947\/rs833061\/rs1570360\/rs2010963\/rs833068\/rs833070) <jats:italic><jats:styled-content style=\"fixed-case\">VEGFA<\/jats:styled-content><\/jats:italic> haplotype analysis identified haplotype 111111 to be negatively (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>\u00a0=\u00a00.68) and haplotype 111222 to be positively (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>\u00a0=\u00a01.89) associated with <jats:styled-content style=\"fixed-case\">VOC<\/jats:styled-content>. rs2010963, rs833068, and rs3025020 were correlated with <jats:styled-content style=\"fixed-case\">VOC<\/jats:styled-content> type, while rs3025020 was correlated with hospitalization, <jats:styled-content style=\"fixed-case\">VOC<\/jats:styled-content> treatment, and duration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Specific <jats:italic><jats:styled-content style=\"fixed-case\">VEGFA<\/jats:styled-content><\/jats:italic> variants contribute to the pathogenesis of <jats:styled-content style=\"fixed-case\">SCD VOC<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.12003","type":"journal-article","created":{"date-parts":[[2012,8,24]],"date-time":"2012-08-24T07:31:21Z","timestamp":1345793481000},"page":"403-409","source":"Crossref","is-referenced-by-count":31,"title":["The relation of vascular endothelial growth factor (<scp>VEGF<\/scp>) gene polymorphisms on <scp>VEGF<\/scp> levels and the risk of vasoocclusive crisis in sickle cell disease"],"prefix":"10.1111","volume":"89","author":[{"given":"Hebah H.","family":"Al\u2010Habboubi","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry Arabian Gulf University Manama Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najat","family":"Mahdi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Salmaniya Medical Complex Manama 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