title: The relation of vascular endothelial growth factor (VEGF) gene polymorphisms on VEGF levels and the risk of vasoocclusive crisis in sickle cell disease.
abstract: OBJECTIVE
  The association of vascular endothelial growth factor (VEGFA) variants and VEGF secretion with sickle cell disease (SCD) vasoocclusive crisis (VOC) was investigated in 210 VOC patients and 114 pain-free control patients.
  
  
  METHODS
  VEGFA -2578C/A (rs699947), -460T/C (rs833061), -1154G/A (rs15703060), -634G/C (rs2010963), 398G/A (rs833068), 497G/A (rs833070), -583T/C (rs3025020), and 936C/T (rs3025039) were carried out by real-time PCR.
  
  
  RESULTS
  Higher frequency of rs2010963 C-allele, rs833068 A-allele, and rs3025020 C-allele and significant differences in rs2010963, rs833068, and rs3025020 genotype distribution were seen in VOC than steady-state patients. Increased VOC risk was seen with rs2010963 as heterozygous and more as homozygous, and in rs833068 and rs3025020 homozygous carriers. While there were no differences in VEGF levels between VOC and steady-state controls, there was a progressive decline in serum VEGF in rs2010963 and rs833068 heterozygous and homozygous genotypes, but an opposite trend was seen in VOC patients. Haploview analysis revealed high LD between rs699947, rs833061, rs1570360, rs2010963, rs833068, and rs833070, but weak or no LD between rs3025020 and rs3025039 and other SNPs. Six-locus (rs699947/rs833061/rs1570360/rs2010963/rs833068/rs833070) VEGFA haplotype analysis identified haplotype 111111 to be negatively (OR = 0.68) and haplotype 111222 to be positively (OR = 1.89) associated with VOC. rs2010963, rs833068, and rs3025020 were correlated with VOC type, while rs3025020 was correlated with hospitalization, VOC treatment, and duration.
  
  
  CONCLUSIONS
  Specific VEGFA variants contribute to the pathogenesis of SCD VOC.
authors.affiliation: Department of Medical Biochemistry, Arabian Gulf University, Manama, Bahrain.
authors.forename: Hebah H
authors.initials: HH
authors.lastname: Al-Habboubi
authors.forename: Najat
authors.initials: N
authors.lastname: Mahdi
authors.forename: Tala M
authors.initials: TM
authors.lastname: Abu-Hijleh
authors.forename: Farah M
authors.initials: FM
authors.lastname: Abu-Hijleh
authors.forename: Mai S
authors.initials: MS
authors.lastname: Sater
authors.forename: Wassim Y
authors.initials: WY
authors.lastname: Almawi
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications* / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012307:Risk Factors; D014652:Vascular Diseases / Q000097:blood / Q000209:etiology* / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics*; D055815:Young Adult
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A