RESUMO
Objective To investigate the relationship between three polymorphic sites of ZNF804A gene and cognitive dysfunction in schizophrenia.Methods Polymerase Chain Reaction (PCR) was used to determine the genotypes and allele frequencies of the three sites (rs1344706,rs12613195 and rs1583048) of ZNF804A gene in 320 patients with schizophrenia (case group) and 324 normal people (control group).The Montreal Cognitive Assessment (MoCA) was used to assess cognitive function.Results (1) The allelic and genotypic distributions in rs1344706 between patients with schizophrenia (T/T,T/G,G/G genotypes:20.3％,50.0％,29.7％),and healthy controls(T/T,T/G,G/G genotypes:13.7％,51.2％,35.1％)had statistically significance(P＞0.05).There was a statistically significant difference in the allele and genotype distribution of rs1344706 between the case group and the control group (P＜0.05),and the family transmission disequilibrium existed in rs1344706 and rs12613195.(2) The MoCA scores in the case group(＜26 points) were lower than those of the control group (P＜0.05).(3)There was a statistically significant difference between the total scores of MoCA (F=202.49,P＜0.05) and scores assessed in different time (F=53.34,P＜ 0.05) in patients with three genotypes of rs1344706.Moreover,the interaction between genotype and time was also statistically significant (F=3.88,P＜0.05),in which the patients with T/T genotype had the lowest total score.(4)There was a statistically significant difference between the total score of MoCA(F=367.78,P ＜0.05) and scores assessed in different time (F=27.35,P＜0.05) in patients with three genotypes of rs12613195,in which the patients with C/C genotype had the lowest total score.However,the interaction between genotype and time was not statistically significant(P＞0.05).(5)The effect of rs1344706 on cognitive function was slightly larger than that of rs12613195.(6)The cognitive function scores of patients carrying rs1344706 and rs12613195 sites decreased year by year.Conclusion ZNF804A gene rs1344706 and rs12613195 may be associated with cognitive dysfunction of schizophrenia,and rs1344706T and rs12613195C may be risk factors for schizophrenia and cognitive impairment.Furthermore,cognitive impairment in patients with rs1344706 is more pronounced and worsened with prolonged condition.rs1583048 may not be associated with cognitive function of schizophrenia.
RESUMO
ZNF804A rs1344706 has been identified as one of the risk genes for schizophrenia. However, the neural mechanisms underlying this association are unknown. Given that ZNF804A upregulates the expression of COMT, we hypothesized that ZNF804A may influence brain activity by interacting with COMT. Here, we genotyped ZNF804A rs1344706 and COMT rs4680 in 218 healthy Chinese participants. Amplitudes of low-frequency fluctuations (ALFFs) were applied to analyze the main and interaction effects of ZNF804A rs1344706 and COMT rs4680. The ALFFs of the bilateral dorsolateral prefrontal cortex showed a significant ZNF804A rs1344706 × COMT rs4680 interaction, manifesting as a U-shaped modulation, presumably by dopamine signaling. Significant main effects were also found. These findings suggest that ZNF804A affects the resting-state functional activation by interacting with COMT, and may improve our understanding of the neurobiological effects of ZNF804A and its association with schizophrenia.
RESUMO
Objective To explore the association between the ZNF804A gene genetic variation poly-morphism rs1344706 and brain structure and function in patients with schizophrenia. Methods Literature search was conducted in Pubmed and other databases,the processes were performed in strict accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,then the Comprehensive Meta-Analysis software was used for meta-analysis. Results Schizophrenia patients with rs1344706 risk al-lele had lager gray matter in the amount of brain regions including frontal lobe (z＝3.445,P＝0.001),tempo-ral lobe (z＝2.140,P＝0.032) and other brain regions; healthy controls with the risk allele had smaller gray matter and regional activity in the frontal lobe ( gray matter: z＝－2.008, P＝0.045, regional activity: z＝－4.036,P＜0.01) and other regions. Sensitivity analysis was stable,but publication bias existed in a few ana-lyses of indexes. Conclusion The risk allele in ZNF804A gene rs1344706 has positive effects on the brain structure in patients with schizophrenia,but negative effects on the brain structure and function in the healthy individuals.