| Objective:The glutamate hypothesis of schizophrenia suggested that the function of glutamate N-methyl-D-aspartate receptors and glutamate neurotransmitters were abnormal.Excitatory amino acid transporters(EAATs)could transport excess glutamate from the synaptic cleft and play an important role in the nervous system.Previous studies have shown that schizophrenia is associated with EAATI and EAAT2 genes.However,no research was found on the relationship between EAAT genes(EAAT1 and EAAT2)and schizophrenia in China.Therefore,a case-control study was conducted to explore the correlation between EAAT genes(EAAT1 and EAAT2)and schizophrenia in Chinese Han population and to investigate the relationship between these two genes polymorphisms and clinical characteristics,severity of symptoms and cognitive dysfunction in schizophrenic patients.Methods:In this study,six SNPs located in functional region(3'untranslated region or 5'untranslated region)were selected by a combination of two methods which combining the SNPs data of EAAT1 and EAAT2 genes from the International Genome Database and The Genome Reference Consortium Human Genome Build 38(GRch38)edition of human genome sequence with the method of screening tagger SNPs from Haploview 4.2 software.A total of 6 SNPs including rs2269272?rs4354668?rs12360706?rs3088168?rs12294045?rs10836387 were selected.Then the 6 SNPs from 233 schizophrenic patients and 342 controls were genotyped by SNaPshot.General demographic data questionnaire was used to collect clinical characteristics.Clinical symptoms were measured by Positive and Negative Syndrome Scale(PANSS)and cognitive function was assessed by Matrics Consensus Cognitive Battery(MCCB).SPSS21.0 software was used for statistical analysis.?2test,one-way ANOVA,non-parametric test and covariance analysis were used to explore the correlation between the two genes polymorphisms and clinical characteristics,severity of symptoms and cognitive impairment in schizophrenic patients.The difference was statistically significant when P<0.05.Results:1.The allele frequency and genotype frequency of EAAT2 rs12294045 were significantly different between case group and control group(allele:X2=8.144,P=0.004;genotype:?2=8.054,P=0.02).There were no significant differences in allele and genotype distribution of the other five SNPs between the two groups.2.There were significant differences among the three genotypes(CC/CT/TT)of EAAT2 rs12294045 in family history distribution(P<0.05)and patients with CT genotype had more family history of schizophrenia.However,there were no significant differences in 10 other clinical characteristics including education level,current marital status,history of schizophrenia,gender,age at the time of consultation,personality,interpersonal relationship,onset form,current occupational status,duration of onset,age of onset,and total score and facor scores of PANSS scale(P>0.05).3.There were statistically significant differences between patients with different genotypes of EAAT2 rs12294045 in MCCB evaluation of verbal memory(P=0.049)and digital sequence(P=0.016).Patients with CT heterozygous genotype had the lowest scores.Conclusions:1.The polymorphism of rs2269272 in EAAT1 gene may have no correlation with schizophrenia in Chinese Han population.2.The polymorphism of rs12294045 in EAAT2 gene may be associated with schizophrenia in Chinese Han population.The mutation of heterozygous CT genotype may increase the risk of schizophrenia.SNPs rs4354668,rs12360706,rs3088168 and rs10836387 may have no correlation with schizophrenia in Chinese Han population.3.The polymorphism of rs12294045 may be related to the cognitive functions of speech memory and operational memory in schizophrenia.CT genotype may be one of the risk factors of patients' dysfunction of speech learning memory and working operational memory. |
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