Association of phospholipase A2 receptor 1 polymorphisms with idiopathic membranous nephropathy in Chinese patients in Taiwan

Abstract

BackgroundIdiopathic 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.MethodsTaiwanese-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.ResultsGenotype 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.ConclusionsOur 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.

HLA-DQA1 and PLA2R1 Polymorphisms and Risk of Idiopathic Membranous Nephropathy

“…Coenen et al (29) found no evidence to support this hypothesis; in a cohort of 95 IMN patients, only 9 patients carried rare sequence variants in the PLA2R1 gene, and only 4 of the 9 patients were among the 60 patients who presented circulating autoantibodies against PLA2R. Our study provides additional support to the previously found associations between IMN and common coding and noncoding variants within PLA2R1 and HLA-DQA1 genes (14,18,19,29). Interestingly, the disease-associated genotype of PLA2R1 (rs4664308) is the common genotype, which was previously reported (14,30).…”

“…Many genes within the HLA locus have previously been associated with IMN (15)(16)(17). Moreover, other SNPs within PLA2R1 have been associated with IMN in Taiwanese and Korean populations (18,19). Additional studies to identify and validate genetic risk factors for IMN in independent populations may help to elucidate its pathogenesis.…”

Phospholipase A2 Receptor (PLA2R1) Sequence Variants in Idiopathic Membranous Nephropathy

“…SNPs in this gene have also been shown to be associated to iMN susceptibility in two candidate gene association studies performed in Korea and Taiwan. 6,7 These findings together suggest an important role for PLA2R1 in the pathogenicity of iMN.…”

“…10,11 The other two nonsynonymous SNPs identified in this study (rs35771982; p.His300Asp and rs3828323; p.Gly1106Ser) have Table 2. Sequence variants in PLA2R1 observed in 60 anti-PLA2R1-positive patients previously been shown, in candidate gene association studies that tested only single SNPs, to be associated with iMN by groups from Taiwan (p.His300Asp) 6 and Korea (p.His300Asp, p.Gly1106Ser). 7 Both SNPs reached significance for allelic association with iMN in the present study (P=1.6310 23 for rs3828323 and P=5.7310 26 for rs35771982) and might be particularly relevant also because they were identified in ethnically distant populations.…”

“…SNP rs4665143 was significantly associated with iMN (P=2.1310 25 ), confirming our previous work. 5 Two nonsynonymous SNPs identified in this study (rs35771982 [p.His300Asp] and rs3828323 [p.Gly1106Ser]) were also assessed by the two candidate gene association studies from Taiwan (p.His300Asp) 6 and Korea (p.His300Asp, p.Gly1106Ser) 7 and found to be significantly associated with iMN. Both SNPs reached significance for allelic association with iMN in the present study (P=1.6310 2 3 for rs3828323 and P=5.7310 26 for rs35771982).…”