Exploring the Genetic Association of the ABAT Gene with Alzheimer's Disease

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	Exploring the Genetic Association of the ABAT Gene with Alzheimer's Disease
	Zheng, QZ; Bi, R; Xu, M; Zhang, DF; Tan, LW; Lu, YP; Yao, YG
	2021
发表期刊	MOLECULAR NEUROBIOLOGY
ISSN	0893-7648
卷号	58 期号:5 页码:1894-1903
摘要	Accumulating evidence demonstrated that GABAergic dysfunction contributes to the pathogenesis of Alzheimer's disease (AD). The GABA aminotransferase (ABAT) gene encodes a mitochondrial GABA transaminase and plays key roles in the biogenesis and metabolism of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter. In this study, we performed an integrative study at the genetic and expression levels to investigate the potential genetic association between the ABAT gene and AD. Through re-analyzing data from the currently largest meta-analysis of AD genome-wide association study (GWAS), we identified genetic variants in the 3'-UTR of ABAT as the top AD-associated SNPs (P < 1 x 10(-4)) in this gene. Functional annotation of these AD-associated SNPs indicated that these SNPs are located in the regulatory regions of transcription factors or/and microRNAs. Expression quantitative trait loci (eQTL) analysis and luciferase reporter assay showed that the AD risk alleles of these SNPs were associated with a reduced expression level of ABAT. Further analysis of mRNA expression data and single-cell transcriptome data of AD patients showed that ABAT reduction in the neuron is an early event during AD development. Overall, our results indicated that ABAT genetic variants may be associated with AD through affecting its mRNA expression. An abnormal level of ABAT will lead to a disturbance of the GABAergic signal pathway in AD brains.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13498
专题	科研部门_疾病机理遗传学和进化医学学科组（姚永刚）昆明动物研究所
推荐引用方式 GB/T 7714	Zheng, QZ,Bi, R,Xu, M,et al. Exploring the Genetic Association of the ABAT Gene with Alzheimer's Disease[J]. MOLECULAR NEUROBIOLOGY,2021,58(5):1894-1903.
APA	Zheng, QZ.,Bi, R.,Xu, M.,Zhang, DF.,Tan, LW.,...&Yao, YG.(2021).Exploring the Genetic Association of the ABAT Gene with Alzheimer's Disease.MOLECULAR NEUROBIOLOGY,58(5),1894-1903.
MLA	Zheng, QZ,et al."Exploring the Genetic Association of the ABAT Gene with Alzheimer's Disease".MOLECULAR NEUROBIOLOGY 58.5(2021):1894-1903.

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