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The relation of vascular endothelial growth factor ( VEGF ) gene polymorphisms on VEGF levels and the risk of vasoocclusive crisis in sickle cell disease
Author(s) -
AlHabboubi Hebah H.,
Mahdi Najat,
AbuHijleh Tala M.,
AbuHijleh Farah M.,
Sater Mai S.,
Almawi Wassim Y.
Publication year - 2012
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12003
Subject(s) - haplotype , vascular endothelial growth factor a , vascular endothelial growth factor , genotype , pathogenesis , medicine , allele , single nucleotide polymorphism , snp , immunology , endocrinology , biology , vegf receptors , genetics , gene
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 −2578 C/A (rs699947), −460 T/C (rs833061), −1154 G/A (rs15703060), −634 G/C (rs2010963), 398 G/A (rs833068), 497 G/A (rs833070), −583 T/C (rs3025020), and 936 C/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 SNP s. Six‐locus (rs699947/rs833061/rs1570360/rs2010963/rs833068/rs833070) VEGFA haplotype analysis identified haplotype 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. Conclusion Specific VEGFA variants contribute to the pathogenesis of SCD VOC .