Regulation of the Late Onset alzheimer's Disease Associated HLA-DQA1/DRB1 Expression

被引：20

作者：

Zhang, Xiaoyu ^{[1
]}

Zou, Meijaun ^{[1
,2
]}

Wu, Yuwei ^{[1
,3
]}

Jiang, Danli ^{[1
]}

Wu, Ting ^{[1
,3
]}

Zhao, Yihan ^{[1
]}

Wu, Di ^{[4
,5
]}

Cui, Jing ^{[6
]}

Li, Gang ^{[1
,7
]}

机构：

[1] Univ Pittsburgh, Aging Inst, Bridgeside Point 1,100 Technol Dr, Pittsburgh, PA 15219 USA

[2] Nanjing Med Univ, Dept Pharmacol, Nanjing, Peoples R China

[3] Cent South Univ, Xiangya Sch Med, Dept Med, Changsha, Peoples R China

[4] Univ N Carolina, Bioinformat & Computat Biol, Chapel Hill, NC USA

[5] Univ N Carolina, Dept Periodontol, Chapel Hill, NC USA

[6] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA

[7] Univ Pittsburgh, Dept Med, Sch Med, Pittsburgh, PA 15219 USA

来源：

AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS | 2022年 / 37卷

关键词：

functional SNPs; post-GWAS functional analysis; Late onset Alzheimer's disease (LOAD); CLASS-II; RISK LOCI; GENES; HLA; MICROGLIA; SUSCEPTIBILITY; METAANALYSIS; VARIANTS;

D O I：

10.1177/15333175221085066

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

(Genome-wide Association Studies) GWAS have identified similar to 42 late-onset Alzheimer's disease (LOAD)-associated loci, each of which contains multiple single nucleotide polymorphisms (SNPs) in linkage disequilibrium (LD) and most of these SNPs are in the non-coding region of human genome. However, how these SNPs regulate risk gene expression remains unknown. In this work, by using a set of novel techniques, we identified 6 functional SNPs (fSNPs) rs9271198, rs9271200, rs9281945, rs9271243, and rs9271247 on the LOAD-associated HLA-DRB1/DQA1 locus and 42 proteins specifically binding to five of these 6 fSNPs. As a proof of evidence, we verified the allele-specific binding of GATA2 and GATA3, ELAVL1 and HNRNPA0, ILF2 and ILF3, NFIB and NFIC, as well as CUX1 to these five fSNPs, respectively. Moreover, we demonstrate that all these nine proteins regulate the expression of both HLA-DQA1 and HLA-DRB1 in human microglial cells. The contribution of HLA class II to the susceptibility of LOAD is discussed.

引用

页数：11

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