Variants in the Promoter Region of HLA-DQA1 were Associated with Idiopathic Membranous Nephropathy in a Chinese Han Population  

作　　者：Xiao-Song Qin Jian-Hua Liu Guan-Ting Lyu Meng-Le Peng Fu-Ning Yang Dong-Chun Qin Yong-Zhe Li Yong Liu 

机构地区：[1] Department of Medical Laboratory, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110011, China [2] Department of Blood Transfusion, Tangdu Hospital, The Fourth Military Medical University, Xi' an, Shaanxi 710038, China [3] Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China [4] Department of Rheumatology and Clinical immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing 100005, China

出　　处：《Chinese Medical Journal》2017年第14期1677-1682,共6页中华医学杂志（英文版）

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.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.

关 键 词：Autoimmune Disease HLA-DQA1 Idiopathic Membranous Nephropathy PROMOTER CHINESE 

分 类 号：Q347[生物学—遗传学] O636[理学—高分子化学]