Rueda Blanca, Perez-Armengol Cristina, Lopez-Lopez Sandra, Garcia-Porrua Carlos, Martín Javier, Gonzalez-Gay Miguel A
Instituto de Parasitología y Biomedicina López Neyra, CSIC, Granada, Spain.
J Rheumatol. 2006 Jan;33(1):69-73.
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.
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.
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).
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.
据报道，过敏性紫癜（HSP）患者循环血管内皮生长因子（VEGF）表达升高。我们研究了VEGF基因功能变异-1154 G→A（rs1570360）和-634 G→C（rs2010963）在HSP易感性中的作用，以确定其与HSP严重全身并发症尤其是肾脏并发症的关联。
对西班牙西北部卢戈地区57例根据拟定标准分类为原发性皮肤血管炎的HSP患者进行研究。所有患者均需至少随访2年。采用基于TaqMan 5'等位基因鉴别分析的实时PCR技术，对患者及种族匹配的对照（n = 226）进行VEGF -1154 G→A和-634 G→C多态性基因分型。
HSP患者与对照之间，未观察到这两种VEGF多态性的等位基因或基因型频率有显著差异。然而，与健康对照相比，患有肾炎的HSP患者中高VEGF产生者的VEGF -1154 G等位基因增加（p = 0.02，比值比2.13，95%可信区间1.11 - 4.08；校正p值 = 0.04）。同样，与对照相比，患有肾炎的患者中高VEGF产生者的VEGF -634 C等位基因增加（p = 0.04，比值比1.66，95%可信区间1.01 - 2.73；校正p值 = 0.08）。-1154G/-634C单倍型与肾炎易感性相关（p = 0.03，比值比1.71，95%可信区间1.01 - 2.89）。观察到-1154A/-634G VEGF启动子单倍型对肾炎有保护作用（p = 0.02，比值比0.49，95%可信区间0.30 - 0.95）。
我们的结果提示，VEGF -1154 G→A和-634 G→C多态性可能与HSP患者肾炎的发生有关。
