An Association Between Schizophrenia And The Single Nucleotide Polymorphism Of PIP3-E And APOD Gene

Schizophrenia is a kind of common mental disorder, which pathogenesis remains undefined. Numerous family, twin, and adoption studies have demonstrated the role of genetic components in the aetiology of schizophrenia. However, major common risk loci have not been found. To map and clone schizophrenia-related genes in humans, is not only helpful to interpret the mechanisms of its molecular genetics, but also establishes the foundation of clinical gene diagnosing and curing diseases in gene's level and drug designing. Therefore, the researches on candidate gene of schizophrenia have always been an important part of aetiology research of schizophrenia. The development of molecular genetic and genetic epidemiology has made it possible to carry on such kind of research, and we have got some achievements. Association analysis which based on trios and makered by SNPs, opens up the possibility of studying the genetic basis of complex disease,such as oncomas,cardiovascular and cerebrovascular diseases,neuro and psychiosis,and it establishes the foundation of preventing,diagnosing and curing diseases on gene's level.APOD and PIP3-E gene have been suggested as a promising candidate for the vulnerability to schizophrenia in view of both its function and location in the genome, thus its polymorhpism probably has association with schizophrenia. In order to detect our hypothesis, five SNPs were genotyped in this study, they were rs2280250(APOD), rs17278409(PIP3-E), rs11155952(PIP3-E), rs17085177(PIP3-E) and rs9371781 (PIP3-E). The study used a family-based analysis in which the family trios,consisting of father, mother and affected offspring. They were all Chinese Han decent in North China. Polymerase chain reaction and restriction fragment length polymorphism (PCR–RFLP)were adopted to examine individual genotype. Statistical software SPSS was used to handle the data on genotype. Goodness of fitχ2 test was used to detect whether the SNPs distribution in the sample population is in Hardy-Weinberg equilibrium. Multifunctional genetic statistical software were used to detect whether the tested SNPs locus was associated with schizophrenia by two family-based association analysis, the haplotype relative risk (HRR) and the transmission disequilibrium test (TDT). Then we determined whether APOD gene and PIP3-E gene was associated with schizophrenia.The analytic results showed that age of schizophrenia was between 14 and 48 yeares old, the mean of age was 25.14±6.568 years old. Most schizophrenia (153) are 20 ~ 29 years old. There were no difference between the male and female schizophrenia with age. There was significant difference between the male and female schizohrenia at the positive clinical symptoms of experience of being revealed, delusion of love, other delusion, illogic of thinking and bizarre behavior ( P < 0.05 ). The incidence rate of the five positive clinical symptoms were higher in female schizophrenia than in male schizophrenia. And there was significant difference between the male and female schizohrenia in the negative clinical symptoms of illogic of thinking and bizarre behavior. Premorbid personality of most schizophrenia was introvert and there was sex differences.The goodness-of-fit test showed that the genotype frequency distributions of these 5 SNPs were not deviated from the Hardy-Weinberg equilibrium. Neither HRR nor TDT showed a genetic association between the 5 SNPs and schizophrenia. Schizophrenia has been characterized heterogeneously in clinical presentation. The clinical heterogeneity may be related to genetic heterogeneity. To validate this hypothesis, we divided the patients into two groups based on the clinical symptoms. With theχ2 test, we can conclude that whether there were some significant differences of the frequencies distribution of allele and genotype in two groups.The results showed that there were correlations between rs2236257 allelic frequencies and some clinical symptoms of schizophrenia, such as delusion of observation, delusion of negation, and incoherence of thinking (P<0.05), and there were correlations between its genotypic frequencies and some clinical symptoms of schizophrenia, such as delusion of observation and delusion of negation (P<0.05).On the whole, The findings of this study suggested that APOD gene and PIP3-E gene family may not play an important role(at least in chinese han population) in schizophrenia development. However,locus rs2236257 is associated with some of the symptoms of schizophrenia. Therefore,its modest effect should not be excluded while the mechanisms need further study.Future directions in schizophrenia genetics research include family-based linkage disequilibrium mapping based on large-scale genotyping of SNP markers and investigations of the epigenetic regulation of genes and the interaction between genes and environment variable may be necessary for complete understanding the genetic components to the aetiology of schizophrenia.