摘要Background:Idiopathic membranous nephropathy (IMN) is an autoimmune disease and the leading cause of adult nephritic syndrome.HLA-DQA1 had been identified to be associated with IMN in Europeans and the result was replicated in Chinese Han population.In this study,six single nucleotide polymorphisms (SNPs) in the promoter ofHLA-DQA I and other two SNPs with IgA nephropathy were included for the association analysis.Methods:The SNPs were genotyped in 509 patients and 601 controls by the MassArray iPLEX.The quantification ofanti-phospholipase A2 receptor (PLA2R) antibodies in sera of IMN patients was performed by anti-PLA2R ELISA (lgG) kit.Results:After analysis,four SNPs were significantly associated with IMN,with rs2187668 and rs28383345 as the top two signals (P =8.42×10-4 and 2.48× 10-5,respectively).Even under dominant model,the two SNPs were still significantly associated with IMN (P =3.50×10-3 for rs28383345 and P =6.55×10-5 for rs2187668).After conditional study with rs2187668,rs28383345 was the only variant significantly correlated with IMN after Bonferroni correction (P =0.016).The minor alleles of the two SNPs were also mutually exclusive in our cohort.This indicated that the two SNPs were independently associated with IMN in Chinese Han population.Levels of anti-PLA2R autoantibodies were correlated with the genotypes of the two SNPs,but not significantly (P＞0.05).Conclusions:Our results revealed that a novel independent variant in the promoter of HLA-DQA I was associated with I MN in Chinese Han population.The locus possessed regulatory role according to the data of RegulomeDB.The exact role of the SNPs on the expression of HLAoDQA1 needs further investigation.