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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.
Eur J Haematol. 2012 Nov; 89(5):403-9.EJ

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.

CONCLUSION

Specific VEGFA variants contribute to the pathogenesis of SCD VOC.

Authors+Show Affiliations

Department of Medical Biochemistry, Arabian Gulf University, Manama, Bahrain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22925497

Citation

Al-Habboubi, Hebah H., et al. "The Relation of Vascular Endothelial Growth Factor (VEGF) Gene Polymorphisms On VEGF Levels and the Risk of Vasoocclusive Crisis in Sickle Cell Disease." European Journal of Haematology, vol. 89, no. 5, 2012, pp. 403-9.
Al-Habboubi HH, Mahdi N, Abu-Hijleh TM, et al. The relation of vascular endothelial growth factor (VEGF) gene polymorphisms on VEGF levels and the risk of vasoocclusive crisis in sickle cell disease. Eur J Haematol. 2012;89(5):403-9.
Al-Habboubi, H. H., Mahdi, N., Abu-Hijleh, T. M., Abu-Hijleh, F. M., Sater, M. S., & Almawi, W. Y. (2012). The relation of vascular endothelial growth factor (VEGF) gene polymorphisms on VEGF levels and the risk of vasoocclusive crisis in sickle cell disease. European Journal of Haematology, 89(5), 403-9. https://doi.org/10.1111/ejh.12003
Al-Habboubi HH, et al. The Relation of Vascular Endothelial Growth Factor (VEGF) Gene Polymorphisms On VEGF Levels and the Risk of Vasoocclusive Crisis in Sickle Cell Disease. Eur J Haematol. 2012;89(5):403-9. PubMed PMID: 22925497.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The relation of vascular endothelial growth factor (VEGF) gene polymorphisms on VEGF levels and the risk of vasoocclusive crisis in sickle cell disease. AU - Al-Habboubi,Hebah H, AU - Mahdi,Najat, AU - Abu-Hijleh,Tala M, AU - Abu-Hijleh,Farah M, AU - Sater,Mai S, AU - Almawi,Wassim Y, Y1 - 2012/08/30/ PY - 2012/07/25/accepted PY - 2012/8/29/entrez PY - 2012/8/29/pubmed PY - 2013/1/11/medline SP - 403 EP - 9 JF - European journal of haematology JO - Eur. J. Haematol. VL - 89 IS - 5 N2 - 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. CONCLUSION: Specific VEGFA variants contribute to the pathogenesis of SCD VOC. SN - 1600-0609 UR - https://www.unboundmedicine.com/medline/citation/22925497/The_relation_of_vascular_endothelial_growth_factor__VEGF__gene_polymorphisms_on_VEGF_levels_and_the_risk_of_vasoocclusive_crisis_in_sickle_cell_disease_ L2 - https://doi.org/10.1111/ejh.12003 DB - PRIME DP - Unbound Medicine ER -