Abstract: Objective: To determine whether functional vascular endothelial growth factor (VEGF) polymorphisms influence the expression of the clinical phenotype of giant cell arteritis (GCA). We also evaluated whether VEGF polymorphism is associated with the development of severe ischaemic manifestations in patients with GCA regardless of the clinical phenotype, classic cranial GCA or predominantly extracranial GCA large-vessel vasculitis (LVV). Methods: VEGF rs833061 T/C, rs2010963 G/C and rs3025039 C/T polymorphisms were genotyped in 185 patients with biopsy-proven cranial GCA, 105 with extracranial LVV-GCA and 490 healthy controls. Allelic combinations (haplotypes) of VEGF were carried out. Comparisons were performed between patients with GCA and healthy controls as well as between patients with GCA stratified according to the clinical phenotype and the presence of severe ischaemic manifestations. Results: No significant differences in genotype, allele, and haplotype frequencies of VEGF were found between patients with GCA and healthy controls as well as between GCA patients with the classic cranial pattern and the extracranial LVV-GCA pattern of the disease. However, the VEGF CGC haplotype (OR= 1.63 [1.05-2.53]) and the CGT haplotype (OR= 2.55 [1.10-5.91]) were significantly more frequent in GCA patients with severe ischaemic complications compared to those patients without these complications. Conclusion: VEGF haplotypes seem to play a role in the development of severe ischaemic manifestations in GCA patients, regardless of the clinical phenotype of expression of the disease.

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