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Variants of the ST6GALNAC2 promoter influence transcriptional activity and contribute to genetic susceptibility to IgA nephropathy
Li, Gui-Sen; Zhu, Li; Zhang, Hong; Lv, Ji-Cheng; Ding, Jia-Xiang; Zhao, Ming-Hui; Shen, Yan; Wang, Hai-Yan
关键词St6galnac2 Haplotype Sialic Acid Iga Nephropathy Promoter
刊名HUMAN MUTATION
2007-10-01
DOI10.1002/humu.20543
28期:10页:950-957
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Genetics & Heredity
研究领域[WOS]Genetics & Heredity
关键词[WOS]MUTATION NOMENCLATURE ; HTSNPS SELECTION ; LINKAGE PHASE ; ASSOCIATION ; GLYCOSYLATION ; CANCER ; TESTS ; CELLS ; GLOMERULONEPHRITIS ; POLYMORPHISMS
英文摘要

IgA nephropathy (IgAN) is a polygenic disorder. Increasing evidence has implicated that aberrant glycosylation of IgA1 molecules, including alpha 2,6 sialic acid defects, are involved in the pathogenesis of IgAN. In the present study, we designed an association study to investigate polymorphisms of two important genes, ST6GALNAC2 and NEU1, which are involved in the sialylation of the IgA1 molecule, in the susceptibility to IgAN. A total of 670 patients with histologically proven IgAN and 494 healthy controls were enrolled. Screening of SNPs in the coding and promoter regions of the ST6GALNAC2 and NEU1 genes was performed by sequencing. ST6-SNPI (c.-988A>G), ST6-SNP2 [rs3840858:D>1(CGGC), c.-450_-449insCGGC], ST6-SNP3 (rs1867561:C>G, c.-135C>G), and ST6-SNP7 (rs2304921:G>A, c. 186 + 12G > A) in the ST6GALNAC2 gene were selected as tagging SNPs. Functional evaluations of targets were assayed by luciferase activity. The alpha 2,6 sialic acid contents of serum IgA1 in 497 patients were analyzed. Our results demonstrated that the frequency of haplotype ADG in the promoter region of ST6GALNAC2 was significantly higher in IgAN patients than that in controls (p = 0.0069; odds ratio [OR] = 1.36; 95% confidence interval [CI], 1.08-1.72). Furthermore, the ADG haplotype was associated with the deficient degrees of a2,6 sialic acid of IgA1 molecules in IgAN patients (r = 0.408, p = 0.0035). The ADG haplotype conferred significantly reduced promoter activity compared with the most common haplotype GDG in vitro (196.43 +/- 21.55 vs. 258.41 +/- 46.25; p = 0.002). In the present study, we identified for the first time the ADG haplotype in the ST6GALNAC2 gene as a functional regulatory variant that may contribute to the genetic susceptibility in a subset of patients in whom the desialylation of IgA1 molecules was the main causative pathogenesis of IgAN.

语种英语
WOS记录号WOS:000250036600006
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被引频次:33[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/57403
专题北京大学第一临床医学院_肾脏内科
作者单位1.Peking Univ, Inst Nephrol, Peking Univ Hosp 1, Div Renal,Dept Internal Med, Beijing 100034, Peoples R China
2.Minist Hlth, Key Lab Renal Dis, Beijing, Peoples R China
3.Chinese Natl Human Genome Ctr, Beijing, Peoples R China
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Li, Gui-Sen,Zhu, Li,Zhang, Hong,et al. Variants of the ST6GALNAC2 promoter influence transcriptional activity and contribute to genetic susceptibility to IgA nephropathy[J]. HUMAN MUTATION,2007,28(10):950-957.
APA Li, Gui-Sen.,Zhu, Li.,Zhang, Hong.,Lv, Ji-Cheng.,Ding, Jia-Xiang.,...&Wang, Hai-Yan.(2007).Variants of the ST6GALNAC2 promoter influence transcriptional activity and contribute to genetic susceptibility to IgA nephropathy.HUMAN MUTATION,28(10),950-957.
MLA Li, Gui-Sen,et al."Variants of the ST6GALNAC2 promoter influence transcriptional activity and contribute to genetic susceptibility to IgA nephropathy".HUMAN MUTATION 28.10(2007):950-957.
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