Association Of Schizophrenia With Genetic Polymorphisms Of Axon Guidance Pathway In Chinese Zhuang And Han Population

Objectives:This study aims to explore the association of five genes (PAK1, PAK2, EPHB1, PPP3CB and PTK2) in axon guidance pathway with schizophrenia susceptibility and its severity of clinical symptoms in Chinese Zhuang and Han population, which provide the basic data of schizophrenia genetic mechanism in these two population.Methods'. A case-control study was performed. The subjects in this study included 700 schizophrenia patients (300 Zhuang and 400 Han) and 700 healthy controls (300 Zhuang and 400 Han). A Sequenom MassARRAY genotyping method was carried out to genetype 7 SNPs (PAK1 genetic variants rs2844337 and rs11237200, PAK2 genetic variant rs1619646 and rs1718408, EPHB1 genetic variant rs11918092, PPP3CB genetic variant rs12644, PTK2 genetic variant rs7460). Positive and Negatives Syndrome Scale (PANSS) was used to assess the severity of clinical symptoms of SCZ patients. Statistical analysis were conducted using SPSS and PLINK.Results:1. Hardy-Weinberg Equilibrium test:In the healthy control groups (Zhuang, Han and the total), the genotypic distributions of all the polymorphisms did not significantly deviate from Hardy-Weinberg Equilibrium (P> 0.050).2. The association of the susceptibility to schizophrenia with genetic ploymorphisms of axon guidance pathway:? The genotypic(P=0.038) and allelic (P=0.033) frequencies of PAK1 genetic variant rs2844337 significantly differed between the patients and the controls in the Chinese Han population but not in the Chinese Zhuang and the total population. By contrast, the genotypic and allelic frequencies of the other six polymorphisms did not significantly differ in either or total of the populations (P> 0.050).? Logistic regression analysis showed that the rs2844337 polymorphism was significantly associated with the the susceptibility to schizophrenia in additive (P=0.036, Padj= 0.032), recessive (P=0.037, Padj=0.031) and allele (P=0.033) models before and after the adjustment of age and gender. However, no significant association of the other six polymorphisms with schizophrenia risk were observed in all the genetic models neither before nor after the adjustment of age and gender (P> 0.050, Padj>0.050).3. The association between the severity of clinical symptoms and genetic ploymorphisms of axon guidance pathway:? In the Chinese Han population, PAK1 genetic variant rs 11237200 was significantly associated with total score (Padj=0.004), positive scale score (Padj =0.010), general psychopathology scale score (Padj=0.007), "thought disorder" (Padj= 0.027), "activation"(Padj=0.007), "paranoid" (Padj=0.016), and "aggressivity" (Padj=0.003) in the recessive model, but rs2844337 polymorphism in PAK1 gene was not associated with clinical symptoms in all the genetic models (Padj>0.050); PAK2 genetic variant rs1619646 significantly affected general psychopathology scale score (Padj= 0.043) in dominant model, and the other variant rs1718408 in this gene was significantly associated with general psychopathology scale score (Padj= 0.027) and "depression" (Padj= 0.021) in recessive model; EPHBl genetic variant rs11918092 was significantly associated with positive scale score (Padj= 0.035) in dominant model; PPP3CB genetic variant rsl2644 significantly affected negative scale score (Padj= 0.032) and "lack of response" (Padj=0.030) in recessive model; PTK2 genetic variant rs7460 was significantly associated with activation score (Padj= 0.032) in recessive model.? In the Chinese Zhuang population, PPP3CB genetic variant rsl2644 was significantly associated with total score (Padj= 0.048), negative scale score (Padj=0.025), general psychopathology scale score (Paaj=0.016), "lack of response" (Padj= 0.020), "activation" (Padj=0.039), and "depression" (Padj= 0.032) in the dominant model; PAK2 genetic variant rs1718408 significantly associated with positive scale score (Padj= 0.012), "thought disorder" (Padj= 0.026), "paranoid" (Padj=0.015), and "aggressivity" (Padj=0.019) in the recessive model. However, no significant association was observed between the severity of clinical symptoms and the following polymorphisms:PAK1 genetic variants rs2844337 and rs11237200, PAK2 genetic variant rsl619646, EPHB1 genetic variant rs11918092, PTK2 genetic variant rs7460 (all Padj>0.050).Conclusion:? PAK1 genetic variants rs2844337 was suggested to be significantly associated with the susceptibility to schizophrenia in Chinese Han population.? The following polymophisms were observed to be associated with the severity of clinical symptoms in different degree:PAK1 genetic variants rs2844337 and rs11237200, PAK2 genetic variant rs1619646 and rs1718408, EPHB1 genetic variant rs11918092, PPP3CB genetic variant rs 12644, PTK2 genetic variant rs7460. Moreover, ethnic difference was observed on the association of these polymorphisms with the severity of clinical symptoms.