The Study Of Genetic Susceptibility To 8p Gene ASAH1 And NRG-1 In Schizophrenia

Objective To explore the genetic susceptibility of ASAH1 gene in schizophrenia. ASAH1 gene was detected by Cui's microarray and was significantly down regulated in all schizophrenia patients.Methods 1.Three SNPs(rs3753118,rs3753116 and rs7830490)of ASAH1 in 254 schizophrenia trios were genotyped by using PCR-RFLP,and the LD,TDT and HHRR were analyzed by using EMLD,UNPHASED and TRANSMIT softwares.2.PANSS was used to quantify the phenotypes of schizophrenia. One-Way ANOVA and the QTPHASE of UNPHASED2.4 were used to compare the PANSS score between different genotypes,alleles and haplotypes.3.Expression levels of ASAH1 in the leukocytes from 28 first-episode drug-naive patients(F-patients),30 recurrent patients taking antipsychotic medication(R-patients)and 30 healthy controls,were measured by using RT-PCR.Results 1.(1)Three SNPs were in H-W equilibrium for all trios(P＞0.05).(2) Strong LD was found between rs3753116 and rs7830490(D'=0.851,r~2=0.369),mild LD was found between rs3753118 and rs3753116(D'=0.495,r~2=0.165),and weak LD between rs3753118 and rs7830490(D'=0.196,r~2=0.029).(3)Three SNPs were observed to be associated with schizophrenia by TDT and HHRR(P＜0.05).(4)The haplotype rs3753118-rs7830490 and rs3753118-rs3753116-rs7830490 were associated with schizophrenia(P＜0.05),and risk haplotype rs3753118T-rs7830490A, rs3753118T-rs3753116G-rs7830490A were identified(P<0.05).2.(1)There were significant difference of the Positive score among patients grouped upon genotypes in rs3753118,and the total PANSS score and Negative score were significant different among patients grouped upon genotypes in rs3753116 (P＜0.05).Patients with the rs3753118 C/C genotype,compared to C/T genotype, demonstrated a higher Positive score and General pathology score.The total PANSS score and Negative score of patients with G/G genotype in rs3753116 were higher than that of A/G genotype,and the Negative score of patients with G/G genotype in rs3753116 was higher than that of A/A genotype(P＜0.05).(2)The total PANSS score and the Negative score of patients with C-G haplotype of rs3753118-rs3753116,with C-G-A haplotype of rs3753118-rs3753116-rs7830490,were higher than that of reference haplotype(P＜0.05).3.(1)The first-episode drug-naive patients(F-patients)were younger than recurrent patients(R-patients)and healthy controls(P＜0.01).(2)The PANSS total score,general score of F-patients were significantly higher than that of R-patients (P＜0.001).(3)ASAH1 expression level was significantly different among F-patients, R-patients and healthy controls(P=0.048),and was higher in F-patients than in R-patients(P=0.017).Although F-patients' ASAH1 expression level was 20.9% higher than healthy controls,R-patients' ASAH1 expression level was 11.9%lower than healthy controls,but all without significant difference(P＞0.05).(4)In R-patients group,the ASAH1 expression level of patients with family history was significant lower than that of patients without family history and healthy control(P=0.013, P=0.009).(5)There were no significant differences on ASAH1 expression levels among positive,negative,compound symptom patient subgroups and healthy control (P＞0.05).(6)There were no significant differences on ASAH1 gene expression levels among mild,severe symptom subgroups and healty control(P＞0.05).(7)Pearson correlate analysis showed that there was no significant correlation between ASAH1 expression level and the score of PANSS(P＞0.05).Conclusions 1.ASAH1 gene was linked with schizophrenia and might be a positional susceptibility gene of schizophrenia.2.There might be symptom quantitative trait locis of schizophrenia on ASAH1 gene.3.The antipsychotics might degrade the ASAH1 expression level of the schizophrenia with mental disorder family history.4.ASAH1 expression level might have no relationship with the types and severity of schizophrenia symptom. Objective To explore the genetic susceptibility of NRG-1 gene in schizophreniaMethods 1.Two tag SNPs(rs2439322 and rs16879809)of NRG-1 in 254 schizophrenia trios were genotyped by using PCR-RFLP,and the LD,TDT and HHRR were analyzed by using EMLD,UNPHASED and TRANSMIT softwares.2.PANSS was used to quantify the phenotypes of schizophrenia. One-Way ANOVA and the QTPHASE of UNPHASED2.4 were used to compare the PANSS score between different genotypes,alleles and haplotypes.Results 1.(1)Two SNPs were in H-W equilibrium for parents(P＞0.05), SNPrs2439322 also in H-W for patients,but SNPrs16879809 was not in H-W for patients(P＜0.01).(2)Weak LD was found between rs2439322 and rs16879809(D' =0.178,r~2=0.024).(3)Two SNPs were not observed to be associated with schizophrenia by TDT and HHRR(P＞0.05).(4)The haplotype rs2439322—rs16879809 was associated with schizophrenia(P＜0.05),and risk haplotype rs2439322C—rs16879809T was identified(P＜0.01).2.(1)There was no significant difference of the PANSS score among patients grouped upon different genotypes,alleles and haplotypes of NRG-1 rs2439322 and rs16879809.Conclusions 1.The NRG-1 rs2439322—rs16879809 haplotype was associated with schizophrenia,and indicated that NRG-1 might be a positional susceptibility gene of schizophrenia.2.There might be no relationship between symptom quantitative trait of schizophrenia and NRG-1 gene. Objective To explore the gene-gene interaction between ASAH1 and NRG-1 who are located in 8p.Methods Utilizing the ASAH1 and NRG-1 genotyped datas of 254 trios in PartⅠand PartⅡ,analyzed the gene-gene interaction between 3 SNPs of ASAH1 (rs3753118,rs3753116 and rs7830490)and 2 SNPs(rs2439322 and rs16879809)of NRG-1 by using MDR software.Results MDR revealed that the pattern with 4 SNPs(rs3753118,rs7830490, rs2439322 and rs16879809)had statistical significance(P<0.05).Conclusions 1.There might exist gene-gene interaction between ASAH1 and NRG-1,and it could increase the risk for schizophrenia.2.The strong linkage signal of 8p might be associated with gene-gene interaction of ASAH1 and NRG-1.8p might be the susceptibility genetic area of schizophrenia and might exist a number of schizophrenia candidate genes.