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

IMR OpenIR

	Variants in the Promoter Region of HLA-DQA1 were Associated with Idiopathic Membranous Nephropathy in a Chinese Han Population
其他题名	Variants in the Promoter Region of HLA-DQA1 were Associated with Idiopathic Membranous Nephropathy in a Chinese Han Population
	Qin XiaoSong 1; Liu JianHua 1; Lyu GuanTing 2; Peng MengLe 3; Yang FuNing 4; Qin DongChun 3; Li YongZhe 4; Liu Yong 1
	2017
发表期刊	Chinese Medical Journal
ISSN	0366-6999
卷号	130 期号:14 页码:1677-1682
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 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.
其他摘要	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 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.
关键词	Autoimmune Disease Medicine R HLA-DQA1 Idiopathic Membranous Nephropathy Promoter Chinese
收录类别	CSCD
语种	英语
CSCD记录号	CSCD:6029132
引用统计	被引频次：1[CSCD] [CSCD记录]
文献类型	期刊论文
条目标识符	http://ir.imr.ac.cn/handle/321006/146929
专题	中国科学院金属研究所
作者单位	1.中国科学院金属研究所 2.中国科学院地球环境研究所 3.郑州大学 4.Chinese Acad Med Sci, Peking Union Med Coll Hosp, Department Rheumatol & Clin Immunol, Beijing 100005, Peoples R China Peking Union Med Coll Hosp Department Rheumatol & Clin Immunol 5.上海市地震局
推荐引用方式 GB/T 7714	Qin XiaoSong,Liu JianHua,Lyu GuanTing,et al. Variants in the Promoter Region of HLA-DQA1 were Associated with Idiopathic Membranous Nephropathy in a Chinese Han Population[J]. Chinese Medical Journal,2017,130(14):1677-1682.
APA	Qin XiaoSong.,Liu JianHua.,Lyu GuanTing.,Peng MengLe.,Yang FuNing.,...&Liu Yong.(2017).Variants in the Promoter Region of HLA-DQA1 were Associated with Idiopathic Membranous Nephropathy in a Chinese Han Population.Chinese Medical Journal,130(14),1677-1682.
MLA	Qin XiaoSong,et al."Variants in the Promoter Region of HLA-DQA1 were Associated with Idiopathic Membranous Nephropathy in a Chinese Han Population".Chinese Medical Journal 130.14(2017):1677-1682.