ABSTRACT
Objective To investigate the association between DNA methylation of matrix metallo-proteinase 9(MMP-9) gene and cognitive function including continuous attention,cognitive flexibility and visuospatial memory in patients with chronic schizophrenia.Methods 71 male schizophrenia patients and 69 healthy controls were recruited and detected their cognitive function.Pyrosequencing was used to determine DNA methylation at CpG site in exon 4 and exon 5 of MMP-9 gene.RT-qPCR was used to detect MMP-9 gene expression.Clinical symptoms were assessed by BPRS.Results (1) Cognitive function including Trail Making Test A,Trail Making Test B,Stroop words only,Stroop colors only,Stroop interference,Spatial Processing Block design and Block Design all scores were significantly lower in schizophrenia patients with schizophrenia than those in health controls (P＜0.01);(2) The MMP-9 gene expression in PBMCs was significantly higher in schizophrenia patients (1.31± 0.48) than that in health control (1.11 ± 0.45,P＜ 0.05).The DNA methylation of CpG4-1,CpG4-2,CpG4-3,CpG4-4,CpG4-5,CpG5-1,CpG5-2,CpG5-4 of MMP-9 gene in schizophrenia patients were lower than those in health controls (P＜0.01).(3)DNA methylation of CpG4-3 was positive correlated with Stroop interference (r=0.324,P＜0.01) in health controls.Correlation analysis showed that DNA methylation of CpG4-1 was negatively correlated with sustained attention function (r =-0.329,P＜0.01),cognitive flexibility (r =-0.337,P＜ 0.01) and visuospatial memory (r =-0.308,P＜ 0.05) in schizophrenia patients.There were positive correlations between DNA methylation of CpG4-5 (r=0.305,P＜0.05),CpG5-1 (r=0.262,P＜0.05),CpG5-3 (r=0.260,P＜0.05),average DNA methylation at exon 5 (r=0.288,P＜0.05) and visuospatial memory.DNA methylation of CpG5-4 was positive correlated with sustained attention function (r=0.251,P＜0.05) and visuospatial memory (r=0.350,P＜ 0.01) respectively.Conclusion Male patients with schizophrenia suffer from extensive cognitive impairment,and methylation of MMP-9 gene may be associated with cognitive impairment of schizophrenia.