An Association Study Of BDNF Gene And MicroRNA Binding With Schizophrenia In Chinese Han Population

Objective:we aimed to explore whether gene BDNF involved in the pathophysiology of schizophrenia in Chinese Han population according to investigate BDNF gene rs6265 Polymorphism and mRNA levels of BDNF gene in the peripheral blood;Besides,we detected expression levels of miR-124-3p, miR-206, miR-132 which binding with gene BDNF in the peripheral blood of schizophrenia and then we conduct a primary discussion for potential molecular regulation mechanism of BDNF involved in schizophrenia;Above all,we try to find out a schizophrenia biomarker and drug target.Methods:The study has two parts and both use case-control study method.The data of first study collected from a GWAS sample which included 1407 schizophrenia patients and 1136 normal controls.we use ?2 test to analyze genotype and allelefrequency between schizophrenia patients and normal controls by SHE.sis software.The second study collected 32 schizophrenia patients and 48 normal controls according to. Peripheral blood samples were collected from all subjects.RT-qPCR was used to analyze the expression levels of BDNF gene, miR-124-3p, miR-206, miR-132.We used The Positive and Negative Syndrome Scale (PANSS) to assess the condition of schizophrenia patients.Then all schizophrenia patients were treated with single atypical antipsychotics for 12 weeks.PANSS was used to reassess patients'recovery condition and we also collected their blood sample to analyze the expression levels of BDNF gene, miR-124-3p, miR-206, miR-132 again. We used R to perform the data processing. The differences of mRNA levels between cases and controls and the differences of mRNA levels between 32 pairs of schizophrenia patients before and after treatment were analyzed using t test.Results:1.There was no significant differences in age, gender between schizophrenia patients and normal controls in the study of the gene expression. (p>0.05).2. Genotypic distributions of the gene BDNF rs6265 did not deviate from Hardy-Weinberg equilibrium (HWE) in either the schizophrenia patient group or the normal control group(P> 0.05).There was a significant difference has been establishment in the allele frequencies between schizophrenia patients and the normal controls(P=0.037). Further gender stratificationfound a significantdifference both in the genotype and allele frequencies in the males(P=0.009, P=0.003).3. The expression levels of BDNF gene and miR-124-3p between schizophrenia patients and normal controls have been found a significant difference (p=5.169e-05, P=5.241e-05). BDNF is under-expressed,whilemiR-124-3p is over-expressed in schizophrenia patients compared with normal controls. No significant differences has been found in the expression levels of miR-206 and miR-132 between two sample groups (P=0.114, P=0.307)4. The PANSS scores show all schizophrenia patients got clinical improvement after 12-week treatment compared with baseline (P<0.05)5. The expression of BDNF was up-regulated after the 12-week treatment (P=1.874e-04),while miR-124-3p down-regulated after the 12-week treatment (P=0.016).And expression levels of BDNF and miR-124-3p have no significant differences compared with normal controls after 12-week treatment (P=0.719,P=0.183).6. Both the expression of miR-206 and miR-132 were decreased after the 12-week treatment (P=2.863e-04, P=0.009).Conclusions:1.BDNF gene rs6265 Polymorphism may havean association with schizophrenia in Chinese Han population, especially in males.2. MRNA of BDNF gene may be involved in the pathophysiology of schizophrenia in Chinese Han population.BDNF gene may be a biomarker of schizophrenia diagnostics and potential target of antipsychotics.3. miR-124-3p may be a strong predictor who regulates the presence of BDNF gene in schizophrenia.4. Expression of miR-206 and miR-132 may have no association with schizophrenia.