Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan.
J Biomed Sci. 2010 Oct 11;17(1):81. doi: 10.1186/1423-0127-17-81.
Idiopathic membranous nephropathy (IMN) is one of the most common forms of autoimmune nephritic syndrome in adults. The purpose of this study is to evaluate whether polymorphisms of PLA2R1 affect the development of IMN.
Taiwanese-Chinese individuals (129 patients with IMN and 106 healthy controls) were enrolled in this study. The selected single nucleotide polymorphisms (SNPs) in PLA2R1 were genotyped by real-time polymerase chain reaction using TaqMan fluorescent probes, and were further confirmed by polymerase chain reaction-restriction fragment length polymorphism. The roles of the SNPs in disease progression were analyzed.
Genotype distribution was significantly different between patients with IMN and controls for PLA2R1 SNP rs35771982 (p = 0.015). The frequency of G allele at rs35771982 was significantly higher in patients with IMN as compared with controls (p = 0.005). In addition, haplotypes of PLA2R1 may be used to predict the risk of IMN (p = 0.004). Haplotype H1 plays a role in an increased risk of IMN while haplotype H3 plays a protective role against this disease. None of these polymorphisms showed a significant and independent influence on the progression of IMN and the risk of end-stage renal failure and death (ESRF/death). High disease progression in patients having C/T genotype at rs6757188 and C/G genotype at rs35771982 were associated with a low rate of remission.
Our results provide new evidence that genetic polymorphisms of PLA2R1 may be the underlying cause of IMN, and the polymorphisms revealed by this study warrant further investigation.
特发性膜性肾病(IMN)是成人中最常见的自身免疫性肾病综合征之一。本研究旨在评估 PLA2R1 多态性是否影响 IMN 的发生。
本研究纳入了台湾汉族个体(129 例 IMN 患者和 106 例健康对照者)。采用 TaqMan 荧光探针实时聚合酶链反应检测 PLA2R1 中的单核苷酸多态性(SNPs),并通过聚合酶链反应-限制性片段长度多态性进一步确认。分析 SNPs 在疾病进展中的作用。
PLA2R1 SNP rs35771982 的基因型分布在 IMN 患者和对照组之间差异有统计学意义(p=0.015)。与对照组相比,IMN 患者 rs35771982 的 G 等位基因频率明显较高(p=0.005)。此外,PLA2R1 的单倍型可能用于预测 IMN 的风险(p=0.004)。单倍型 H1 增加了 IMN 的发病风险,而单倍型 H3 对该疾病具有保护作用。这些多态性均未显示对 IMN 进展和终末期肾衰竭和死亡(ESRF/death)风险有显著的独立影响。rs6757188 的 C/T 基因型和 rs35771982 的 C/G 基因型的患者疾病进展较高与缓解率较低相关。
我们的研究结果提供了新的证据,表明 PLA2R1 基因多态性可能是 IMN 的潜在原因,本研究中发现的多态性值得进一步研究。