Genetic Association Between The Polymorphism Of KPNB3 Genes And Schizophrenia

Schizophrenia is a serious mental disorder with a lifetime prevalence rate of 1% in the general population worldwide. It was characterized by the abnormal mental functions and disturbed behavior,which characteristically appear as a series of clinical features,such as positive and negative symptoms,and disturbances in basic cognitive functions. The recurrence rate and mutilation rate of schizophrenia are very high,and the large suffering population has brought heavy economic burden to the society and families, threatening the safety and stability of society. Several lines of evidence from epidemiological data suggest that genetic factors are likely to play an essential role in the developing of schizophrenia. Schizophrenia is not a simple Mendelian disease but looks like a complex disease involving several genes, with each susceptible gene having only a modest individual effect. Basically, there are two steps for mapping a disease-related gene in the human genome, the linkage-based genome-wide scan and the regional mapping with linkage disequilibrium (LD) analysis. Genome-wide scanning shows that all the chromosomes except for chromosome 19, 21 and Y,may contain a schizophrenia susceptibility gene, while there are only 6 chromosome regions whose positive regions could have a better reproducibility. They are1q21-22,5q22-23,6p24-21,8p22-21,13q14-33 and 22q11-12.The present study selected schizophrenia patients and unrelated healthy control individuals as objects from Han Chinese in 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.The differences of alleic gene and genotype distribution between the schizophrenia patients and control group were detected byχ2 test. Then we determined whether KPNB3 gene was associated with. schizophrenia.Three SNPs were genotyped in this study, they were rs626716, rs2761072和rs624066,The goodness-of-fit test showed that the genotype frequency distributions of these 3 SNPs were not deviated from the Hardy-Weinberg equilibrium. Theχ~2 test showed that the frequency distributions of alleic gene and genotype for these three SNPs were found no significant differences between the schizophrenia patients and control group. 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 theχ~2 test, we can conclude that whether there were some significant differences of the frequencies distribution of allele and genotype in two groups. And we can see this difference in the frequency distribution of rs626716 locus when we analyzed the positive symptom of Delusion of influence (χ~2=4.613, P =0.032). It is suggested that there was an association between rs626716 locus and one of the psychotic symptoms of Delusion of influence. And we can see the difference in the frequency distribution of rs2761072 locus when we analyzed the positive symptom of Delusion of being revealed (χ~2=4.263,P=0.039). Also we can suggest that there was an association between rs624066 locus and one of the psychotic symptoms of Delusion of being revealed. Also we can see the difference in the frequency distribution of rs624066 locus when we analyzed the positive symptom of Delusion of being revealed (χ2=6.563, P=0.010). With the same reason, we can suggest that there was an association between rs624066 locus and one of the psychotic symptoms of Delusion of being revealed. Distribution of genotype frequency on rs624066 locus had a significant difference in schizophrenia with symptoms of Delusion of being revealed. Also with symptoms of Delusion of love.As we all known, paranoid and undifferentiated patients account for the most part of the subgroup, so we analyzed the association between the two locus and the two kinds of schizophrenia. In the analysis between two SNPs and all the psychotic symptoms of paranoid and undifferentiated patients, we can see many positive results. With them, we can confirm that the different heterogeneities in the disease.The findings of this study suggested that KPNB3 gene may not play an important role in schizophrenia development. However,it may be associated with some of the positive symptoms of schizophrenia. Therefore, its modest effect should not be excluded while the mechanisms need further study.