Alzheimer's disease (AD) is affected by genetic factors. Polymorphisms in the glutathione S-transferase 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 characterize the mechanisms underlying regulation of Gsto1 variation regulation and to identify network members that may contribute to AD risk or progression. Allele-specific assays confirmed that variation in Gsto1 expression is controlled by cis-expression quantitative trait loci. We found that Gsto1 mRNA levels were related to several central nervous system traits, such as glial acidic fibrillary protein levels in the caudate putamen, cortical 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, Grin2b, Ide, and Psenen. To evaluate the relationships between Gsto1 and candidate network members, we transfected astrocytes with Gsto1 siRNA and assessed the effect on putative downstream effectors. We confirmed that knockdown of Gsto1 had a significant influence on Pa2g4 expression, suggesting that Pa2g4 may be a downstream effector of Gsto1, and that both genes interact with other genes in a network during AD pathogenesis.

Yue Jia;Meng-Die Gao;Yun-Fang Liu;Lu Lu;Gang Chen;Ying Chen

Department of Histology and Embryology,Medical College,Nantong University,Nantong,Jiangsu Province,China;Key Laboratory of Neuroregeneration of Jiangsu and the Ministry of Education,Co-innovation Center of Neuroregeneration,Nantong University,Nantong,Jiangsu Province,China;Department of Genetics,Genomics and Informatics,University of Tennessee Health Science Center,Memphis,TN,USA;Department of Anesthesiology,Affiliated Hospital of Nantong University,Nantong,Jiangsu Province,China

中国神经再生研究（英文版）

[1]Yue Jia;Meng-Die Gao;Yun-Fang Liu;Lu Lu;Gang Chen;Ying Chen-.Genetic dissection of glutathione S-transferase omega-1: identification of novel downstream targets and Alzheimer 's disease pathways)[J].中国神经再生研究（英文版）,2022(11):2452-2458

Gsto1,mossy,Grin2b,Ide,Psenen,Pa2g4

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