WITHDRAWN: DNA methylation and gene expression of matrix metalloproteinase-9 gene in Deficit and Non-Deficit Schizophrenia

Abstract

// Ju Gao 1, 2, * , Hongwei Yi 3, * , Xiaowei Tang 4, * , Xiaotang Feng 5 , Miao Yu 1 , Weiwei Sha 4 , Xiang Wang 6 , Xiaobin Zhang 4 and Xiangrong Zhang 1, 7 1 Department of Geriatric Psychiatry, Nanjing Brain Hospital, Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, China 2 Centers of Disease Prevention and Control for Mental Disorders, Shanghai Changning Mental Health Center, Shanghai 200335, China 3 Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China 4 Department of Psychiatry, Affiliated WuTaiShan Hospital of Medical College of Yangzhou University, Yangzhou, Jiangsu 225003, China 5 Department of Psychiatry, Nanjing Qing Long Mountain Psychiatric Hospital, Nanjing, Jiangsu 211123, China 6 Medical Psychological Institute of the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China 7 Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, Jiangsu 210009, China * These authors contributed equally to this work Correspondence to: Xiangrong Zhang, email: drxrz@hotmail.com Keywords: deficit schizophrenia; matrix metalloproteinase-9; DNA methylation; gene expression; negative symptoms Received: July 31, 2017 Accepted: December 05, 2017 Published: January 02, 2018 ABSTRACT Background: The biological pathology of deficit schizophrenia (DS) remains unclear. Matrix metalloproteinase-9 (MMP-9) might be associated with neural plasticity and glutamate regulation, involved in schizophrenia pathogenesis. This study explored gene expression and DNA methylation of MMP-9 in peripheral blood mononuclear cells (PBMCs) and their relationship with clinical symptoms in DS and non-deficit schizophrenia (NDS). Materials And Methods: Pyrosequencing was used to determine DNA methylation at CpG sites in exon 4 and exon 5 of MMP-9 gene in 51 DS patients, 53 NDS patients and 50 healthy subjects (HC). RT-qPCR was used to detect MMP-9 gene expression. Clinical symptoms were assessed by BPRS, SANS and SAPS scales. Results: MMP-9 gene expression in PBMCs was significantly higher in DS than NDS and HC subjects. Compared to NDS patients, DS patients had significantly lower DNA methylation at individual CpG sites in exon 4 and exon 5 of MMP-9 gene. Correlation analysis showed that DNA methylation in exon 4 was negatively correlated with gene expression in DS group. Positive correlation was found between MMP-9 gene expression and negative symptoms in total schizophrenic patients. The social amotivation factor of SANS and negative syndrome of BPRS was negatively correlated with DNA methylation of CpG5-1 in DS patients but not in NDS patients. Conclusions: DS patients showed a specific abnormality of peripheral MMP-9 gene expression and DNA methylation, indicating a pathological mechanism underlying DS as a specific subgroup of schizophrenia.