FCGR2B 和 FCRLB 基因多态性与 IgA 肾病相关。
FCGR2B and FCRLB gene polymorphisms associated with IgA nephropathy.
机构信息
Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, PR China.
出版信息
PLoS One. 2013 Apr 12;8(4):e61208. doi: 10.1371/journal.pone.0061208. Print 2013.
BACKGROUND
IgA nephropathy (IgAN) is a complex syndrome characterized by deposition of IgA and IgA containing immune complexes (ICs) composed of IgG and complement C3 proteins in the mesangial area of glomeruli. The low-affinity receptors for the Fc region of IgG (FcγRs) are involved in autoantibody/immune complex-induced organ injury as well as ICs clearance. The aim of the study was to associate multiple polymorphisms within FCGR gene locus with IgAN in a large Chinese cohort.
PATIENTS AND METHODS
60 single nucleotide polymorphisms (SNPs) spanning a 400 kb range within FCGR gene locus were analyzed in 2100 DNA samples from patients with biopsy proven IgAN and healthy age- and sex-matched controls from the same population in Chinese.
RESULTS
Among the 60 SNPs investigated, 15 gene polymorphisms within FCGR gene locus (25%) were associated with susceptibility to IgAN. The most significantly associated SNPs within individual genes were FCGR2B rs12118043 (p = 8.7410(-3), OR 0.76, 95% CI 0.62-0.93), and FCRLB rs4657093 (p = 2.2810(-3), OR 0.77, 95% CI 0.65-0.91). Both conditional analysis and linkage disequilibrium analysis suggested they were independent signals associated with IgAN. Associations between FCGR2B rs12118043 and proteinuria (p = 3.65×10(-2)) as well as gross hematuria (p = 4.53×10(-2)), between FCRLB rs4657093 and levels of serum creatinine (p = 2.67×10(-2)) as well as eGFR (p = 5.41*10(-3)) were also observed. Electronic cis-expression quantative trait loci analysis supported their possible functional significance, with protective genotypes correlating lower gene expressions.
CONCLUSION
Our data from genetic associations and expression associations revealed potentially pathogenic roles of Fc receptor gene polymorphisms in IgAN.
背景
IgA 肾病（IgAN）是一种复杂的综合征，其特征是 IgA 及含有 IgG 和补体 C3 蛋白的 IgA 免疫复合物（ICs）在肾小球系膜区沉积。低亲和力 IgG Fc 区受体（FcγRs）参与自身抗体/免疫复合物诱导的器官损伤以及 ICs 的清除。本研究旨在在中国人群中，将 FCGR 基因座内的多个多态性与 IgAN 相关联。
患者和方法
在来自 2100 名经活检证实的 IgAN 患者和同一人群中年龄和性别匹配的健康对照者的 2100 份 DNA 样本中，分析了跨越 FCGR 基因座 400kb 范围的 60 个单核苷酸多态性（SNPs）。
结果
在所研究的 60 个 SNP 中，FCGR 基因座内的 15 个基因多态性（25%）与 IgAN 的易感性相关。在个体基因内最显著相关的 SNP 是 FCGR2B rs12118043（p=8.7410(-3)，OR 0.76，95%CI 0.62-0.93）和 FCRLB rs4657093（p=2.2810(-3)，OR 0.77，95%CI 0.65-0.91）。条件分析和连锁不平衡分析均表明，它们是与 IgAN 相关的独立信号。FCGR2B rs12118043 与蛋白尿（p=3.65×10(-2)）和肉眼血尿（p=4.53×10(-2)）之间存在关联，FCRLB rs4657093 与血清肌酐水平（p=2.67×10(-2)）和 eGFR（p=5.41*10(-3)）之间也存在关联。电子顺式表达定量性状基因座分析支持了它们可能的功能意义，保护基因型与较低的基因表达相关。
结论
我们的遗传关联和表达关联数据揭示了 Fc 受体基因多态性在 IgAN 中的潜在致病作用。
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