Association Study Of Brain-derived Neurotrophic Factor Gene Polymorphisms With Schizophrenia And Its Cognitive Function

Background and Objective: Schizophrenia(SCZ)is a serious and lifelong mental disorder with severe cognitive dysfunction and its etiology remains unknown.Brain-derived neurotrophic factor(BDNF)plays a key role in the process of synaptic remodeling in cognitive processing,affecting the development of various neural processes,such as neuronal differentiation,axon growth and neuron survival.Accumulating evidence has shown that BDNF gene Single Nucleotide Polymorphism(SNP)may be involved in the pathogenesis of schizophrenia.Moreover,BDNF gene SNP may influence specific aspects of human cognitive function.This study aimed to investigate the potential association of BDNF gene SNP with susceptibility to schizophrenia and cognitive function in patients with schizophrenia in Han Chinese population.Methods: In this study,we enrolled 354 schizophrenics(the case group)and 416 healthy control subjects(the control group).Four SNPs(rs7482257,rs7483883,rs1491850 and rs16917234)of BDNF gene were genotyped by Taq Man genotyping technique.The genotype and allele distribution frequency differences were compared between the two groups.The linkage disequilibrium analysis was performed on four SNPs,and the differences in the frequency of haplotype distribution were compared between the two groups.We use Repeatable Battery for the Assessment of Neuropsychological Status(RBANS)to evaluate the cognitive function of 354 schizophrenics and 136 healthy control subjects.Further study,we compared the difference of cognitive function between different genotypes in four SNPs of BDNF gene.Results: 1.Deviation of the genotype was in accordance with the Hardy-Weinberg equilibrium in the two groups(P > 0.05).The genotype and allele frequencies in the four SNPs of BDNF gene between the two groups had no statistically significant differences.2.Linkage disequilibrium analysis and haplotype genetic correlation analysis showed that rs7482257 and rs7483883,rs16917234 and rs1491850 had strong linkage,respectively.The haplotype distribution frequency had no significant differences between the two groups(P>0.05).3.The factor scores and the total score of RBANS of schizophrenics were significantly lower than healthy control subjects(P < 0.001).The cognitive function in schizophrenics showed significant differences between different genotypes of rs7482257(P<0.05).The Schizophrenics with CC genotypes presented lower scores than those with CT genotype(P = 0.03)and TT genotype(P = 0.01)in visuospatial performance,and there was no such difference in healthy control subjects.The differences of the factor scores and the total score of RBANS in schizophrenics and healthy control subjects between the genotypes of BDNF rs7483883,rs1491850 and rs16917234 were not statistically significant(P>0.05).Conclusions: 1.Schizophrenics have extensive cognitive impairment.2.The four SNPs(rs7482257,rs7483883,rs1491850,rs16917234)of BDNF gene may not be susceptible loci to SCZ.3.The CC genotype of rs7482257 in BDNF gene may be associated with visuospatial impairment of SCZ.