FcγRIIa polymorphism:: a susceptibility factor for immune complex-mediated lupus nephritis in Brazilian patients
FcγRIIa polymorphism:: a susceptibility factor for immune complex-mediated lupus nephritis in Brazilian patients
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DOI：
10.1093/ndt/gfh121
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发表时间：
2004-06-01
影响因子：
6.1
通讯作者：
Monteiro, RC
中科院分区：
文献类型：
--
作者：
Bazilio, AP;Viana, VST;Monteiro, RC
背景Fc γ RIIa是一种低亲和力受体，具有两个共显性表达的等位基因8131和H131，其结合免疫球蛋白G（IgG）亚类的能力不同。表达H131的细胞比表达8131变体的细胞更有效地结合复合的IgG 2和IgG 3。Fc γ RIIa多态性已显示与狼疮性肾炎相关。在这里，我们通过比较狼疮性肾炎患者FcgammaRIIa受体的基因型和等位基因分布与巴西种族匹配的健康对照，评估FcgammaRIIa基因多态性与狼疮免疫复合物（IC）介导的肾炎发生的相关性。系统性红斑狼疮（SLE）患者119例，健康志愿者48例。用等位基因特异性引物通过PCR进行Fc γ RIIa基因分型以区分两种等位基因形式（H 131和R131）。SLE肾炎患者与对照组FcgammaRIIa-R131基因型分布比较，FcgammaRIIa-R131纯合性显著增加（P <0.02）。狼疮性肾炎患者的基因型分布（Fc γ RIIa-R/R131为45%，H/R131为30%，H/H131为25%）与对照组（Fc γ RIIa-R/R131为21%，H/R131为52%，H/H131为27%）不同。相比之下，FcgammaRIIa基因型在无肾炎狼疮组和对照组中的分布没有差异（P = 0.3）。进一步证实Fc γ RIIa多态性在IC介导的肾炎中的相关性，与正常对照组（47%）相比，肾功能衰竭患者中8131等位基因（70%）过度表达（P = 0.06）。在狼疮性肾炎中观察到的FcgammaRIIa基因型的偏态分布和纯合R/R131基因型的优势强调了其作为巴西狼疮患者IC介导的肾损伤的遗传风险因素的重要性。
Background. FcgammaRIIa is a low affinity receptor that has two co-dominantly expressed alleles, 8131 and H131, which differ in their ability to bind immunoglobulin G (IgG) subclasses. Cells expressing H131 bind more efficiently complexed IgG2 and IgG3 than those expressing the 8131 variant. The FcgammaRIIa polymorphism has been shown to be associated with lupus nephritis. Here we evaluated the relevance of FcgammaRIIa gene polymorphism in the development of lupus immune complex (IC)-mediated nephritis by comparing the genotype and allelic distribution of this receptor in lupus nephritis to ethnically matched healthy controls in Brazilians.Methods. 119 systemic lupus erythematosus (SLE) patients and 48 healthy volunteers were recruited. FcgammaRIIa genotyping was performed by PCR with allele-specific primers to distinguish between the two allelic forms (H 131 and R131).Results. Comparison of FcgammaRIIa genotypes distribution in SLE patients with nephritis and in controls showed a significant increase in FcgammaRIIa-R131 homozygosity (P less than or equal to 0.02). The genotype distribution in lupus nephritis (45% with FcgammaRIIa-R/R131, 30% with H/R131 and 25% with H/H131) was distinct from that observed in controls (21% with FcgammaRIIa-R/R131, 52% with H/R131 and 27% with H/H131). In contrast, there was no difference in the distribution of FcgammaRIIa genotypes in lupus without nephritis and controls (P = 0.3). Reinforcing the relevance of FcgammaRIIa polymorphism in IC-mediated nephritis, patients with renal failure had an over-representation of the 8131 allele (70%) when compared with normal controls (47%) (P = 0.06).Conclusions. The skewed distribution of FcgammaRIIa genotypes with the predominance of homozygous R/R131 genotype observed in lupus nephritis emphasizes its importance as a heritable risk factor for IC-mediated renal injury in Brazilian lupus patients.