Phospholipase A2 Receptor (PLA2R1) Sequence Variants in Idiopathic Membranous Nephropathy
Phospholipase A2 Receptor (PLA2R1) Sequence Variants in Idiopathic Membranous Nephropathy
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DOI：
10.1681/asn.2012070730
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发表时间：
2013-04-01
影响因子：
13.6
通讯作者：
Ronco, Pierre
中科院分区：
文献类型：
--
作者：
Coenen, Marieke J. H.;Hofstra, Julia M.;Ronco, Pierre
磷脂酶A2的m型受体（PLA2R1）是特发性膜性肾病（iMN）的主要靶抗原。我们最近的全基因组关联研究表明，HLA-DQA1和磷脂酶A2受体（PLA2R1）等位基因的遗传变异与活检证实的iMN最显著相关，这表明PLA2R1基因编码区域内的罕见遗传变异可能有助于抗体的形成。在这里，我们对95名活检证实的iMN白人患者的PLA2R1进行了测序，并通过Sanger测序评估了PLA2R1的所有30个外显子，包括典型（GT-AG）剪接位点。60例患者血清中有抗PLA2R1或肾组织中检测到PLA2R1抗原。我们确定了18个序列变异，其中2个以前没有描述过，7个报道为罕见变异(
The M-type receptor for phospholipase A2 (PLA2R1) is the major target antigen in idiopathic membranous nephropathy (iMN). Our recent genome-wide association study showed that genetic variants in an HLA-DQA1 and phospholipase A2 receptor (PLA2R1) allele associate most significantly with biopsy-proven iMN, suggesting that rare genetic variants within the coding region of the PLA2R1 gene may contribute to antibody formation. Here, we sequenced PLA2R1 in a cohort of 95 white patients with biopsy-proven iMN and assessed all 30 exons of PLA2R1, including canonical (GT-AG) splice sites, by Sanger sequencing. Sixty patients had anti-PLA2R1 in serum or detectable PLA2R1 antigen in kidney tissue. We identified 18 sequence variants, comprising 2 not previously described, 7 reported as rare variants (