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Year : 2017  |  Volume : 130  |  Issue : 14  |  Page : 1677-1682

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

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

Correspondence Address:
Xiao-Song Qin
Department of Medical Laboratory, Shengjing Hospital of China Medical University, 36# Sanhao Street, Heping District, Shenyang, Liaoning 110004
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0366-6999.209884

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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 of HLA-DQA1 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 of anti-phospholipase A2 receptor (PLA2R) antibodies in sera of IMN patients was performed by anti-PLA2R ELISA (IgG) kit. Results: After analysis, four SNPs were significantly associated with IMN, with rs2187668 and rs28383345 as the top two signals (P = 8.42×10-5 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-DQA1 was associated with IMN 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 HLA-DQA1 needs further investigation.

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