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Variants in the Promoter Region of HLA-DQA1 were Associated with Idiopathic Membranous Nephropathy in a Chinese Han Population
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 polymorphi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Medknow Publications & Media Pvt Ltd
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520554/ https://www.ncbi.nlm.nih.gov/pubmed/28685717 http://dx.doi.org/10.4103/0366-6999.209884 |
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author | Qin, Xiao-Song Liu, Jian-Hua Lyu, Guan-Ting Peng, Meng-Le Yang, Fu-Ning Qin, Dong-Chun Li, Yong-Zhe Liu, Yong |
author_facet | Qin, Xiao-Song Liu, Jian-Hua Lyu, Guan-Ting Peng, Meng-Le Yang, Fu-Ning Qin, Dong-Chun Li, Yong-Zhe Liu, Yong |
author_sort | Qin, Xiao-Song |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5520554 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Medknow Publications & Media Pvt Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-55205542017-08-04 Variants in the Promoter Region of HLA-DQA1 were Associated with Idiopathic Membranous Nephropathy in a Chinese Han Population Qin, Xiao-Song Liu, Jian-Hua Lyu, Guan-Ting Peng, Meng-Le Yang, Fu-Ning Qin, Dong-Chun Li, Yong-Zhe Liu, Yong Chin Med J (Engl) Original Article 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. Medknow Publications & Media Pvt Ltd 2017-07-20 /pmc/articles/PMC5520554/ /pubmed/28685717 http://dx.doi.org/10.4103/0366-6999.209884 Text en Copyright: © 2017 Chinese Medical Journal http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. |
spellingShingle | Original Article Qin, Xiao-Song Liu, Jian-Hua Lyu, Guan-Ting Peng, Meng-Le Yang, Fu-Ning Qin, Dong-Chun Li, Yong-Zhe Liu, Yong Variants in the Promoter Region of HLA-DQA1 were Associated with Idiopathic Membranous Nephropathy in a Chinese Han Population |
title | Variants in the Promoter Region of HLA-DQA1 were Associated with Idiopathic Membranous Nephropathy in a Chinese Han Population |
title_full | Variants in the Promoter Region of HLA-DQA1 were Associated with Idiopathic Membranous Nephropathy in a Chinese Han Population |
title_fullStr | Variants in the Promoter Region of HLA-DQA1 were Associated with Idiopathic Membranous Nephropathy in a Chinese Han Population |
title_full_unstemmed | Variants in the Promoter Region of HLA-DQA1 were Associated with Idiopathic Membranous Nephropathy in a Chinese Han Population |
title_short | Variants in the Promoter Region of HLA-DQA1 were Associated with Idiopathic Membranous Nephropathy in a Chinese Han Population |
title_sort | variants in the promoter region of hla-dqa1 were associated with idiopathic membranous nephropathy in a chinese han population |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520554/ https://www.ncbi.nlm.nih.gov/pubmed/28685717 http://dx.doi.org/10.4103/0366-6999.209884 |
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