69 Association Between Functional Haplotypes of Vascular Endothelial Growth Factor and Renal Complications in Henoch-Schönlein Purpura BLANCA RUEDA, CRISTINA PEREZ-ARMENGOL, SANDRA LOPEZ-LOPEZ, CARLOS GARCIA-PORRUA, JAVIER MARTÍN, and MIGUELA. GONZALEZ-GAY ABSTRACT. 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 vas- culitis 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 geno- typed 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 polymor- phisms 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; p c = 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; p c = 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. (J Rheumatol 2006;33:69–73) Key Indexing Terms: HENOCH-SCHÖNLEIN PURPURA DISEASE SUSCEPTIBILITY RENAL INVOLVEMENT VASCULAR ENDOTHELIAL GROWTH FACTOR GENE POLYMORPHISMS From the Instituto de Parasitología y Biomedicina López Neyra, CSIC, Granada; and the Division of Rheumatology, Hospital Xeral-Calde, Lugo, Spain. B. Rueda, PhD; C. Perez-Armengol, PhD; J. Martin, MD, PhD, Instituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC; S. Lopez-Lopez, MD; C. Garcia-Porrua, MD; M.A. Gonzalez-Gay, MD, PhD, Division of Rheumatology, Hospital Xeral-Calde. Dr. Gonzalez-Gay and Dr. Martin share senior authorship in this study. Address reprint requests to Dr. M.A. Gonzalez-Gay, Rheumatology Division, Hospital Xeral-Calde, c) Dr. Ochoa s/n, 27004, Lugo, Spain. E-mail:miguelaggay@hotmail.com Accepted for publication August 31, 2005. Henoch-Schönlein purpura (HSP) is the most common pri- mary small blood vessel leukocytoclastic vasculitis in chil- dren and a rare condition in adults 1 . Palpable purpura and joint and gastrointestinal (GI) manifestations are typical of this vasculitis 2 . Renal manifestations constitute the most feared complications, and longterm morbidity and mortality in HSP are mainly due to renal involvement 3 . Well documented reports of families of first-degree rela- tives with HSP support a genetic component in the patho- genesis of HSP 1,3 . Susceptibility to HSP and associated clin- ical heterogeneity in HSP may be conferred by a number of genetic loci. Studies in Northwestern Spain have shown that different genes may influence the phenotype and the out- come of this condition 4-9 . Vascular endothelial growth factor (VEGF) is a heparin- binding growth factor mainly produced by activated mono- cytes/macrophages and T cells, specific for vascular endothelial cells, which is able to induce angiogenesis in vivo 10 . VEGF stimulates functional changes in endothelial cells and enhances endothelial cell proliferation, angiogene- sis, microvascular permeability to fluids and plasma pro- teins, and monocyte chemotaxis. In addition, it activates interstitial collagenase production and von Willebrand fac- tor release and enhances procoagulant activity 10-14 . As with other systemic vasculitides 15,16 , high expression of circulating VEGF has been reported in patients with leukocytoclastic vasculitis 17 . Interestingly, Topaloglu, et al found a significant increase in the plasma concentrations of VEGF in 22 children with HSP in the acute phase of the dis- ease 18 . However, plasma VEGF levels failed to show any Personal non-commercial use only. The Journal of Rheumatology Copyright © 2006. All rights reserved. Rueda, et al: VEGF polymorphisms in HSP www.jrheum.org Downloaded on November 21, 2022 from