| 1 | Psychiatr. Genet. 2004 Sep 14: 173-6 |
|---|---|
| PMID | 15318034 |
| Title | No association of TAP2 polymorphisms in Korean patients with schizophrenia. |
| Abstract | Polymorphisms of transporters associated with antigen-processing (TAP) genes might influence the susceptibility to精神分裂症by altering the antigen-processing pathway. The aim of this study was to verify the relationship between精神分裂症and the polymorphisms ofTAP2genes. Two hundred and fifty-seven Korean patients diagnosed with精神分裂症according to DSM-IV and 184 normal controls participated in this study.TAP2polymorphic residues at positions 379, 565 and 665 were typed using amplification refractory mutation system-polymerase chain reaction single-strand conformation polymorphism. Distribution of the alleles and genotypes in patients with精神分裂症was not significantly different from those of controls. This study did not show the association of theTAP2gene with精神分裂症in the Korean population. |
| SCZ Keywords | 精神分裂症, schizophrenic |
| 2 | Med. Hypotheses 2009 May 72: 535-8 |
| PMID | 19217216 |
| Title | Transporter associated with antigen processing and the chaperone tapasin: are non-classical HLA genes keys to the pathogenesis of schizophrenia? |
| Abstract | 精神分裂症is a mind-destructive disease. Family and twin studies have indicated an equal contribution of genetic endowment and environmental factors in the pathogenesis of精神分裂症. Recently Chlamydiaceae species has been identified as a major factor in the pathogenesis of精神分裂症, suggesting defective immune responses of精神分裂症patients against this environmental factor. Immune responses against Chlamydiaceae species are controlled by immunogenetic factors. Successful responses against microbes depend on the presentation of immunogenic peptides by HLA molecules, which are encoded by a highly polymorphic gene system. Until now several HLA alleles or HLA antigens have been found associated with精神分裂症by some researchers but not by others. This could be explained by failing immune responses against different microbes or different immune responses against the same microbe. Another explanation, not contradictory rather supplementary, is the participation of non-classical HLA genes in the immune response and thus in the disease development. Variants of these genes, i.e. alleles, which control transportation and loading of microbial peptides onto HLA molecules, could prevent clearing of immune cell infection by selection of non-immunogenic peptides for HLA presentation. To generate support for our hypothesis we determined in a small group of精神分裂症patients and control individuals allele frequencies of the transporter proteins TAP1/TAP2, which select the immunoproteasome-tailored peptides for transportation. We determined also frequencies of TAPASIN alleles, which encode chaperons and also may select peptides for loading on MHC molecules. Our pilot study included 20 patients and 162 control individuals. We found significant associations between精神分裂症and TAP1 allele frequencies (P=9.95x10(-3), chi(2)=12.36) as well as TAPASIN allele frequencies (P=2.8x10(-2), chi(2)=5.3). This suggests that variants of these two genetic systems could influence the disease process of精神分裂症. Furthermore, these genes belong to the family of ABC transporter proteins and may also influence the efficiency of drugs and thus of therapeutic modalities. Our investigations require certainly larger patient panels to prove our hypothesis and our results to be correct. |
| SCZ Keywords | 精神分裂症, schizophrenic |
| 3 | Med. Hypotheses 2009 May 72: 535-8 |
| PMID | 19217216 |
| Title | Transporter associated with antigen processing and the chaperone tapasin: are non-classical HLA genes keys to the pathogenesis of schizophrenia? |
| Abstract | 精神分裂症is a mind-destructive disease. Family and twin studies have indicated an equal contribution of genetic endowment and environmental factors in the pathogenesis of精神分裂症. Recently Chlamydiaceae species has been identified as a major factor in the pathogenesis of精神分裂症, suggesting defective immune responses of精神分裂症patients against this environmental factor. Immune responses against Chlamydiaceae species are controlled by immunogenetic factors. Successful responses against microbes depend on the presentation of immunogenic peptides by HLA molecules, which are encoded by a highly polymorphic gene system. Until now several HLA alleles or HLA antigens have been found associated with精神分裂症by some researchers but not by others. This could be explained by failing immune responses against different microbes or different immune responses against the same microbe. Another explanation, not contradictory rather supplementary, is the participation of non-classical HLA genes in the immune response and thus in the disease development. Variants of these genes, i.e. alleles, which control transportation and loading of microbial peptides onto HLA molecules, could prevent clearing of immune cell infection by selection of non-immunogenic peptides for HLA presentation. To generate support for our hypothesis we determined in a small group of精神分裂症patients and control individuals allele frequencies of the transporter proteins TAP1/TAP2, which select the immunoproteasome-tailored peptides for transportation. We determined also frequencies of TAPASIN alleles, which encode chaperons and also may select peptides for loading on MHC molecules. Our pilot study included 20 patients and 162 control individuals. We found significant associations between精神分裂症and TAP1 allele frequencies (P=9.95x10(-3), chi(2)=12.36) as well as TAPASIN allele frequencies (P=2.8x10(-2), chi(2)=5.3). This suggests that variants of these two genetic systems could influence the disease process of精神分裂症. Furthermore, these genes belong to the family of ABC transporter proteins and may also influence the efficiency of drugs and thus of therapeutic modalities. Our investigations require certainly larger patient panels to prove our hypothesis and our results to be correct. |
| SCZ Keywords | 精神分裂症, schizophrenic |
| 4 | Eur Arch Psychiatry Clin Neurosci 2012 Apr 262: 199-205 |
| PMID | 22120873 |
| Title | Case-control association study for 10 genes in patients with schizophrenia: influence of 5HTR1A variation rs10042486 on schizophrenia and response to antipsychotics. |
| Abstract | The aim of this study is to investigate possible associations between a set of single-nucleotide polymorphisms (SNPs) within 10 genes with精神分裂症(SCZ) and response to antipsychotics in Korean in-patients treated with antipsychotics. Two hundred and twenty-one SCZ in-patients and 170 psychiatrically healthy controls were genotyped for 42 SNPs within ABCB1, ABCB4,TAP2, CLOCK, CPLX1, CPLX2, SYN2, NRG1, 5HTR1A and GPRIN2. Baseline and final clinical measures, including the Positive and Negative Symptoms Scale (PANSS), were recorded. Rs10042486 within 5HTR1A was associated with both SCZ and clinical improvement on PANSS total scores as well as on PANSS positive and PANSS negative scores. The haplotype analyses focusing on the four, three and two blocks' haplotypes within 5HTR1A confirmed such findings as well. We did not observe any significant association between the remaining genetic variants under investigation in this study and clinical outcomes. Our preliminary findings suggest that rs10042486 within 5HTR1A promoter region could be associated with SCZ and with clinical improvement on PANSS total, positive and negative scores in Korean patients with SCZ. However, taking into account the several limitations of our study, further research is needed to draw more definitive conclusions. |
| SCZ Keywords | 精神分裂症, schizophrenic |
| 5 | J Psychiatr Res 2014 Mar 50: 73-8 |
| PMID | 24365204 |
| Title | Protein-interaction-network-based analysis for genome-wide association analysis of schizophrenia in Han Chinese population. |
| Abstract | 精神分裂症is a severe neuropsychiatric disorder with a strong and complex genetic background. Recent genome-wide association studies (GWAS) have successfully identified several susceptibility loci of精神分裂症. In order to interpret the functional role of the genetic variants and detect the combined effects of some of these genes on精神分裂症, protein-interaction-network-based analysis (PINBA) has emerged as an effective approach. In the current study, we conducted a PINBA of our previous GWAS data taken from the Han Chinese population. In order to do so, we used dense module search (DMS), a method that locates densely connected modules for complex diseases by integrating the association signal from GWAS datasets into the human protein-protein interaction (PPI) network. As a result, we identified one gene set with a joint effect significantly associated with精神分裂症和基因表达图谱分析表明that they were mainly neuro- and immune-related genes, such as glutamatergic gene (GRM5), GABAergic genes (GABRB1, GABARAP) and genes located in the MHC region (HLA-C,TAP2, HIST1H1B). Further pathway enrichment analysis suggested that these genes are involved in processes related to neuronal and immune systems, such as the Adherens junction pathway, the Neurotrophin signaling pathway and the Toll-like receptor signaling pathway. In our study, we identified a set of susceptibility genes that had been missed in single-marker GWAS, and our findings could promote the study of the genetic mechanisms in精神分裂症. |
| SCZ Keywords | 精神分裂症, schizophrenic |