The Association Between Phospholipase A2 Receptor,HLA Complex Class ? HLA-DQ?-chain 1 Single Nucleotide Polymorphisms And Idiopathic Membranous Nephropathy In Sichuan

Objective:Polymorphisms of PLA2R1 and HLA-DQA1 are closely associated with IMN and several variants of SNP have been reported to affect IMN susceptibility.In China,the association was reported only in BeijingandTaiwan.EightSNPsofPLA2RandoneSNP ofHLA-DAQ1which were reported previously were included in our study to analysis the impact of single locus effects and gene-gene interaction of IMN in Sichuan.Method:Blood samples were collected from 314 patients with IMN diagnosed by renal biopsy and 354 healthy controls.PCR-sequence-based typing technique was used to analyze the distribution of alleles in IMN and healthy controls and Chi-square test was used to compare frequency between two groups.Logistic regression was used to analyze the effects of each SNP on the susceptibility of IMN under the dominant,recessive and additive models.Clinical data were collected and the effects of SNP on different clinical manifestations were analyzed.Bonferroni correction was used to adjust the P values for multiple testing.P value of less than 0.05 was considered statistically significant.Result:Significantly different frequencies of rs4664308,rs2715918,rs4665143,rs35771982,rs3749119,rs2187668 alleles were observed between IMN and control group.A allele of rs2715918(OR=1.66,95%CI:1.22-2.24,P~?=7.9E-3),A allele of rs4665143(OR=1.76,95%CI:1.41-2.18,P~?=2.7E-6)and A allele of rs2187668(OR=3.29,95%CI:2.30-4.70,P~?=8.0E-11)were risk factors for IMN.Susceptibility of IMN significantly increased with rs2715918 in recessive model(OR=3.114,95%CI:1.203-8.060,P~?=0.16),rs4665143 in recessive model(OR=2.134,95%CI:1.510-3.016,P~?=1.4E-4)and rs2187668 in dominant model(OR=3.961,95%CI:2.679-5.855,P~?=4.1E-11).SignificantdecreaseofIMN susceptibility was observed in rs4664308 in recessive model(OR=0.282,95%CI:0.138-0.577,P~?=4.2E-3),rs3828323 in dominant model(OR=0.625,95%CI:0.454-0.862,P~?=0.03),rs35771982 in recessive model(OR=0.261,95%CI:0.123-0.550,P~?=3.4E-3)and rs3749119 in recessive model(OR=0.232,95%CI:0.111-0.496,P~?=8.8E-4).The haplotype AC of rs2715918 and rs3749119 was a dangerous haplotype of IMN(OR=1.585,95%CI:1.106-2.273,P=4.2E-5).The haplotype ATAC of rs2715918,rs6757188,rs4665143,rs3749119 was a dangerous haplotype of IMN(OR=1.453,95%CI:0.973-2.204,P=3.0E-4).Interaction of rs2715918GA/AA,rs4665143 GA/AA and rs2187668 GA/AA could significantly increase the susceptibility of IMN(OR=10.613,95%CI:4.714-23.895,P=4.0E-10).Different frequencies of rs2715918,rs4665143 and rs2187668alleles were not related to the clinical manifestations of IMN patients.Conclusion:The influence of SNP on susceptibility of IMN in Sichuan Province is inconsistent with those in northern China,other Asian countries and Europe.A allele of rs2715918,rs4665143 and rs2187668 were risk factors for IMN susceptibility and the interaction of the above three alleles could increase the susceptibility.Haplotype can affect the susceptibility of IMN.Haplotype can affect the susceptibility of IMN.