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OBJECTIVE: High expression of circulating vascular endothelial growth factor (VEGF) has been reported in patients with Henoch-Schönlein purpura (HSP). We investigated the role of -1154 G-->A (rs1570360) and -634 G-->C (rs2010963) VEGF gene functional variants in the susceptibility to HSP, to identify associations with severe systemic complications of HSP, in particular with renal complications. METHODS: Fifty-seven patients from the Lugo region of Northwest Spain with primary cutaneous vasculitis classified as HSP according to proposed criteria were studied. All patients were required to have had at least 2 years' followup. Patients and ethnically matched controls (n = 226) were genotyped for the VEGF -1154 G-->A and -634 G-->C polymorphisms using real-time PCR technology based on TaqMan 5' allelic discrimination assay. RESULTS: No significant differences in the allele or genotype frequencies for the 2 VEGF polymorphisms were observed between HSP patients and controls. However, the high VEGF producer VEGF -1154 G allele was increased in HSP patients with nephritis compared with healthy controls (p = 0.02, OR 2.13, 95% CI 1.11-4.08; pc = 0.04). Similarly, the high VEGF producer VEGF -634 C allele was increased in patients with nephritis compared to controls (p = 0.04, OR 1.66, 95% CI 1.01-2.73; pc = 0.08). The -1154G/-634C haplotype was associated with susceptibility to nephritis (p = 0.03, OR 1.71, 95% CI 1.01-2.89). A protective effect against nephritis was observed for the -1154A/-634G VEGF promoter haplotype (p = 0.02, OR 0.49, 95% CI 0.30-0.95). CONCLUSION: Our results suggest a potential implication of the VEGF -1154 G-->A and -634 G-->C polymorphisms in the development of nephritis in patients with HSP.