Association Study Of DTNBP1 Single Nucleotide Polymorphisms With Schizophrenia In Chinese Han Population

Background Schizophrenia is a serious mental disease with complex and variable symptoms.The lifetime prevalence rate in the population is about 1%,which imposes a huge burden on society and families.Due to lack of pathological markers,the etiology and pathogenesis of this disease is currently unknown.Studies have shown that genetic factors play an important role in the pathogenesis of schizophrenia.It is considered that schizophrenia is a complex and multigenic disease.With the technique development of research,a large number of susceptibility sites(lq21-22,6p22-24,8p21-22 etc.)and susceptibility genes(DISC1,COMT,BDNF,RELN etc.)were found.DTNBP1 gene encoding dysbindin-1is located in susceptible locus,which is associated with nerve signal transduction,synapse structure,and neural development.But the results of the association study between the gene and schizophrenia are incongruous.Objectives 1.The relationship between SNP of DTNBP1 gene and schizophrenia susceptibility was performed in a case-control study at Han population of North Henan province.To explore whether these 14 SNPs could be schizophrenia susceptibility sites.2.To investigate the association between the genotype of 14 SNPs of DTNBP1 gene and the clinical symptoms in Chinese Han schizophrenia.Methods 1.Using a case-control study method,900 patients with schizophrenia in the Han population of North Henan province were recruited,which were selected according to the diagnostic criteria for schizophrenia in the Diagnostic and Statistical Manual for Mental Disorders of the United States(DSM-IV-TR).A group of 528 paranoid schizophrenic patients who met the enrollment were included as a case group;900 healthy Han people were included in the same area at the same time,and 528 cases that matched the age and gender of the case group were selected as the normal control group.2.General information and peripheral venous blood of all enrolled personnel were collected.Blood specimen stored at-80°C ultra-low temperature refrigerator.3.Using Positive and Negative Symptom Scale(PANSS)evaluated 228 first-episode schizophrenia patients at the time of enrollment.4.Genomic DNA was extracted from leukocytes using the Relax Gene Blood DNA System(Tiangen Biotech,Beijing,China).5.Genotyping of 14 SNPs was performed using Illumina Golden Gate assays on a Bead Station 500 G Genotyping System.6.Allele frequencies and genotype frequencies of the 14 SNP sites in the case-control group were analyzed by gplink V2.05 software,as well as the analysis of Hardy-Weinberg equilibrium.The linkage disequilibrium analysis and haplotype analysis of SNP sites were performed Haploview V4.1 software.7.Using the SPSS20.0 statistical software to analyze differences between DTNBP1 genotypes and scores of five factors from the PANSS,with the method of ANOVA.Results 1.There are no significant difference in general demographic data such as age and gender between case and control group(P>0.05).2.All of the 14 SNPs loci selected by the institute had been genotyped.The success rate of sample genotyping was 99.84%.3.The genotype distributions,both in patients and controls,were found to be without deviation from HWE equilibrium for any of SNPs.Allele frequencies and genotype frequencies of rs742106 loci were statistically different between the case and the control group(P<0.05).No significant differences were found in the distribution of allele frequencies or genotype frequencies in the other 13 sites.4.In male group,all genotype distributions were found meet with HWE equilibrium.The genotype frequencies and allele frequencies of the 3 sites(rs742106,rs4712253 and rs9370823)were found statistically significant in case and control group(P<0.05);2 sites in the female group did not meet the HWE equilibrium in control group;among the remaining 12 sites,only the rs9358063 locus has significant difference between case and control group(P<0.05).5.There are two linkage disequilibrium regions composed of 14 sites,only one haplotype(G-A-A)has statistically significant between the case and the control group(P<0.05).6.The correlation analysis between genotypes of SNPs and clinical symptoms showed that only rs742106 genotype was significantly associated with PANSS total score,negative factors,depression/anxiety factor scores and excitement/hostility factors in schizophrenia(P<0.05).Conclusions 1.Our results confirmed that DTNBP1 gene is associated with schizophrenia in Han population of North Henan province and may be a risk gene of schizophrenia.2.There is a gender difference in the susceptibility of DTNBP1 gene to schizophrenia.3.DTNBP1 gene is associated with the clinical symptoms of schizophrenia patients and may contribute to the development of schizophrenia.