Glyoxalase 1 Confers Susceptibility to Schizophrenia: From Genetic Variants to Phenotypes of Neural Function

作者：Jingwen Yin, Guoda Ma, Shucun Luo, Xudong Luo, Bin He, Chunmei Liang, Xiang Zuo, Xusan Xu, Qing Chen, Susu Xiong, Zhiyuan Tan, Jiawu Fu, Dong Lv, Zhun Dai, Wen Xia, Dongjian Zhu, Xiaoqing Ye, Zhixiong Lin, Juda Lin, You Li, Wubiao Chen, Zebin Luo, Keshen Li, Yajun Wang · 发表于：Frontiers in Molecular Neuroscience · 年份：2021 · DOI：10.3389/fnmol.2021.739526 · 被引用次数：12 · 研究领域：Genetic Associations and Epidemiology、Glycosylation and Glycoproteins Research、Metabolomics and Mass Spectrometry Studies

This research aimed to investigate the role of glyoxalase 1 (Glo-1) polymorphisms in the susceptibility of schizophrenia. Using the real-time polymerase chain reaction (PCR) and spectrophotometric assays technology, significant differences in Glo-1 messenger ribonucleic acid (mRNA) expression ( P = 3.98 × 10 −5 ) and enzymatic activity ( P = 1.40 × 10 −6 ) were found in peripheral blood of first-onset antipsychotic-naïve patients with schizophrenia and controls. The following receiver operating characteristic (ROC) curves analysis showed that Glo-1 could predict the schizophrenia risk ( P = 4.75 × 10 −6 in mRNA, P = 1.43 × 10 −7 in enzymatic activity, respectively). To identify the genetic source of Glo-1 risk in schizophrenia, Glo-1 polymorphisms (rs1781735, rs1130534, rs4746, and rs9470916) were genotyped with SNaPshot technology in 1,069 patients with schizophrenia and 1,023 healthy individuals. Then, the impact of risk polymorphism on the promoter activity, mRNA expression, and enzymatic activity was analyzed. The results revealed significant differences in the distributions of genotype ( P = 0.020, false discovery rate (FDR) correction) and allele ( P = 0.020, FDR correction) in rs1781735, in which G > T mutation significantly showed reduction in the promoter activity ( P = 0.016), mRNA expression, and enzymatic activity (P = 0.001 and P = 0.015, respectively, GG vs. TT, in peripheral blood of patients with schizophrenia) of Glo-1. The expression quantitative trait locus...