Genetic dissection of glutathione S-transferase omega-1:identification of novel downstream targets and Alzheimer's disease pathways  

作　　者：Yue Jia Meng-Die Gao Yun-Fang Liu Lu Lu Gang Chen Ying Chen 

机构地区：[1]Department of Histology and Embryology,Medical College,Nantong University,Nantong,Jiangsu Province,China [2]Key Laboratory of Neuroregeneration of Jiangsu and the Ministry of Education,Co-innovation Center of Neuroregeneration,Nantong University,Nantong,Jiangsu Province,China [3]Department of Genetics,Genomics and Informatics,University of Tennessee Health Science Center,Memphis,TN,USA [4]Department of Anesthesiology,Affiliated Hospital of Nantong University,Nantong,Jiangsu Province,China

出　　处：《Neural Regeneration Research》2022年第11期2452-2458,共7页中国神经再生研究（英文版）

基　　金：the Natural Science Foundation of China,Nos.81200828(to YC),32070998(to GC);the Key Research and Development Program(Social Development)of Jiangsu Province,No.BE2020667(to GC);the Foundation of Jiangsu Province"333 Project High-level Talents",No.BRA2020076(to GC);the Priority Academic Program Development of Jiangsu Higher Education Institutes(PAPD)。

摘　　要：Alzheimer's disease(AD)is affected by genetic factors.Polymorphisms in the glutathione S-transfe rase omega-1(Gsto1)gene have been shown by genetic correlation analyses performed in different ethnic populations to be genetic risk factors for AD.Gene expression profile data from BXD recombinant inbred mice were used in combination with genetic and bioinformatic analyses to chara cterize the mechanisms underlying regulation of Gstol variation regulation and to identify network membe rs that may contribute to AD risk or progression.Allele-specific assays confirmed that variation in Gstol expression is controlled by cis-expression quantitative trait loci.We found that Gstol mRNA levels were related to several central nervous system traits,such as glial acidic fibrillary protein levels in the caudate putamen,co rtical gray matter volume,and hippocampus mossy fiber pathway volume.We identified 2168 genes whose expression was highly correlated with that of Gsto1.Some genes were enriched for the most common neurodegenerative diseases.Some Gsto1-related genes identified in this study had previously been identified as susceptibility genes for AD,such as APP,Grin2 b,Ide,and Psenen.To evaluate the relationships between Gstol and candidate network members,we transfected astrocytes with Gstol siRNA and assessed the effect on putative downstream effecto rs.We confirmed that knockdown of Gstol had a significant influence on Pa2g4 expression,suggesting that Pa2g4 may be a downstream effector of Gstol,and that both genes intera ct with other genes in a network during AD pathogenesis.

关 键 词：Alzheimer's disease BXD recombinant inbred mice CO-EXPRESSION correlation analysis expression quantitative trait locus expression variation genetic dissection glutathione S-transferase omega-1 HIPPOCAMPUS proliferation-associated 2G4 

分 类 号：R749.16[医药卫生—神经病学与精神病学]