| Objective:(1) To explore the association of MMP-9, DNMT1, DNMT3A, DNMT3B polymorphisms with schizophrenia in Chinese Han population.(2)After the delemination of gender factor, explore the association of MeCP2polymorphisms with female schizophrenia in Chinese Han population.(3)To explore the relationship between the gene-gene interaction of DNMTs and the susceptibility of schizophrenia in Chinese Han population.Methods:(1) As to locus rs3918242on gene MMP-9,SNP genotyping was performed using PCR-RFLP in298schizophrenia patients fulfilled with DSM-â…£-TR criteria for schizophrenia and in298healthy controls. Chi square test was used to compare the inter-group differences of genotypic and allelic distribution.(2) Gene polymorphism analysis using the technology based on micro-array Chip was performed in487schizophrenia patients fulfilled with DSM-â…£-TR criteria for schizophrenia and in496healthy controls,6locus located in the genes including DNMT1,DNMT3A,DNMT3B. Chi square test was used to compare the inter-group differences of genotypic and allelic distribution. Haplotype case-control association analysis based on linkage disequilibrium were conducted using SNP stats online software after the data was screened.The significance of results was corrected by permutation test(3)487schizophrenia patients fulfilled with DSM-IV-TR criteria for schizophrenia and496healthy controls were divided into two groups according to their gender, Gene polymorphism analysis using the technology based on micro-array Chip was performed to analyze5locus located in the gene MeCP2.Chi square test was used to compare the inter-group differences of genotypic and allelic distribution. Haplotype case-control association analysis based on linkage disequilibrium were conducted using SNP stats online software after the data was screened.The significance of results was corrected by permutation test(4)Multifactor dimensionality reduction(MDR) was used to detect DNMT1,DNMT3A,DNMT3B gene-gene interaction in schizophrenia patients. Model with the highest testing accuracy,the significant testing result and the highest CV consistency was regarded as the best.Results:(1)To the point of Locus rs3918242which located in Gene MMP-9, the prevalence of C/C,(C/T+T/T)reached significant difference (P=0.036) between case and control. The prevalence of the allelic C and T between two groups also reached significant difference(P=0.046).(2)To the point of Locus rs2228612which located in Gene DNMT1,the percentage of genotype G/A in case group is36.2%,while in control group is42.9%,the difference between two groups reached significant(P=0.031).(3)To the point of Locus rs11887120which was located in Gene DNMT3A,the distribution of genotype T/T of the two groups reached significant difference (P=0.045).During the male population, the distribution prevalence of Haplotype GTTC is0.3037in case group, and0.2558in control group, P value is0.0058, reached significant difference.(4)To the point of Locus rs1616369which located in Gene MeCP2,the distribution of the genotype G/A between two female groups reached significance(P=0.031).rs3027933,genotype G/C,P value is0.034and rs2239464,in dominant model, genotype A/A also reached significance, P value is0.024.rs17435, genotype T/A,P value is 0.027.rs1734792,genotype C/A,P value is0.0083,in dominant model, the distribution of the genotype A/A between two groups reached significant difference, P value is0.0035. During the female population, the distribution prevalence of Haplotype GCCA is0.1581in case group, and0.2389in control group, P value is0.025, reached significant difference.(5)MDR analysis revealed that the six-loci genotypic combination(rs6119954-rs11887120-rs13420827-rs6511685-rs2228612-r s1550117) was the best gene-gene interaction model of DNMTs in schizophrenia(testing accuracy is0.4822, CV consistency is10/10,P value<0.0001).Conclusion:(1Polymorphism C(-1562)T in MMP-9might be associated with the onset of schizophrenia,MMP-9gene is likely to be susceptibility gene of schizophrenia.(2)Locus rs2228612in DNMT1might be associated with the onset of schizophrenia,DNMT1is likely to be susceptibility gene of schizophrenia.(3)Genotype T/T of Locus rs11887120in DNMT3A might be associated with the onset of schizophrenia, the distribution prevalence of Haplotype GTTC is higher in case group, maybe the susceptibility factor (4)As to female MeCP2gene, the genotype G/A of Locus rs1616369, the genotype G/C of rs3027933,the genotype C/A of rs1734792,the genotype A/A of rs2239464,the genotype T/A of rs17435might associated with the onset of schizophrenia,MeCP2might be susceptibility gene of femaleschizophrenia. The distribution prevalence of Haplotype GCCA is lower in female case group(P=0.025), the Haplotype maybe the protective factor.(5)Through the research of MDR,the interaction of gene DNMT1, DNMT3A,DNMT3B may be associated with the onset of schizophrenia, the interaction may enhance the possibility of schizophrenia's onset.
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