Variation in complement factor H affects complement activation in immunoglobulin A vasculitis with nephritis
Variation in complement factor H affects complement activation in immunoglobulin A vasculitis with nephritis
复制标题
补体因子 H 的变异影响免疫球蛋白 A 血管炎伴肾炎的补体激活。
DOI：
10.1111/nep.13580
复制
发表时间：
2020-01-01
期刊：
影响因子：
2.5
通讯作者：
Zhang, Hong
中科院分区：
文献类型：
--
作者：
Jia, Meng;Zhu, Li;Zhang, Hong
背景免疫球蛋白A(IgA)、肾炎血管炎(IgAVN)和IgA肾病(IgAN)被广泛认为是相关疾病。相当多的证据支持补体激活参与了IgAVN和IgAN的概念。我们以前的研究通过全基因组关联研究发现补体因子H(CFH)的一个遗传变异rs6677604是一个IgAN易感变异，并进一步证实了它与CFHR3-1 Delta的连锁，并证实了它对补体激活从而影响IgAN易感性的影响。目的探讨rs6677604在IgAVN补体激活中的作用。方法入选IgAVN患者632例，IgAN患者1178例，健康对照组902例。Rs6677604的基因分型采用TaqMan等位基因鉴别法或从全基因组关联研究数据中提取。结果IgAVN组rs6677604-A等位基因频率明显高于IgAN组。而IgAVN组与对照组比较，差异无统计学意义。IgAVN患者补体因子H(FH)水平高于IgAN患者，且循环FH水平与C3水平呈正相关。在IgAVN和IgAN中，rs6677604-A与肾小球C3沉积强度降低有关。与IgAVN患者rs6677604-A频率较高一致，IgAVN患者肾小球C3沉积强度低于IgAN患者。结论CFH(Rs6677604)基因变异与IgAVN和IgAN的补体激活表型有关。此外，rs6677604可能是导致IgAVN和IgAN补体激活强度差异的原因之一。
Background Immunoglobulin A (IgA) vasculitis with nephritis (IgAVN) and IgA nephropathy (IgAN) are widely considered as related diseases. Considerable evidences support the notion of involvement of complement activation in both IgAVN and IgAN. Our previous studies identified a genetic variant in complement factor H (CFH), rs6677604, as an IgAN-susceptible variant by genome-wide association study, and further confirmed its linkage toCFHR3-1 Delta and proved its influence on complement activation and thereby on IgAN susceptibility. Aim To explore the role of rs6677604 in complement activation of IgAVN. Methods In this study, we enrolled 632 patients with IgAVN, 1178 patients with IgAN and 902 healthy controls. The genotype of rs6677604 was measured by TaqMan allele discrimination assays or was extracted from genome-wide association study data. Results The frequency of the rs6677604-A allele was significantly higher in IgAVN than in IgAN. However, no significant differences were observed between IgAVN and the controls. Higher complement factor H (FH) levels were observed in IgAVN than IgAN, and positive correlation between circulating FH and C3 levels was present in IgAVN. In both IgAVN and IgAN, rs6677604-A was associated with less intensity of glomerular C3 deposits. In agreement with the higher frequency of rs6677604-A in IgAVN, the glomerular C3 deposits of patients with IgAVN were less intense than those in IgAN. Conclusion Our findings suggest that genetic variation inCFH(rs6677604) is involved in the phenotype of complement activation in both IgAVN and IgAN. Moreover, rs6677604 might contribute to the difference of complement activation intensity between IgAVN and IgAN.