| 1 | Brain Behav. Immun. 2009 Mar 23: 347-50 |
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| PMID | 18848621 |
| Title | CTLA-4 single-nucleotide polymorphisms in a Caucasian population with schizophrenia. |
| Abstract | Associations between a single-nucleotide polymorphism (SNP) in exon 1 of the cytotoxic T-lymphocyte antigen-4 (CTLA4) gene andschizophrenia以前在韩国的人口described. The current study investigated whether a similar link occurs in a Caucasian population withschizophrenia. One hundred and twenty-two age- and sex-matched pairs of people with DSM-III-R diagnosis ofschizophreniaand healthy controls were included in this study. Three previously described SNPs (from the promoter, exon 1 and 3' UTR) of theCTLA4gene were analysed. In the entire sample, we detected no allelic or genotypic association for any of the three SNPs. Given documented gender differences in incidence ofschizophrenia, we conducted separate analyses of male and female participants. In males, both the promoter region SNP (-318C/T) and the 3' UTR SNP demonstrated nominally significant association withschizophrenia. The 3' UTR SNP remained significant following correction for multiple testing (permuted P=0.046). In addition, all possible haplogenotypes showed significant association with disease in males with two--both containing the 3' UTR SNP--remaining significant following correction for the genotypic tests of all SNPs and haplogenotypes in males. These results suggest a role for the 3' UTR SNP and/or variants in high linkage disequilibrium with this SNP in the pathogenesis ofschizophrenia. |
| SCZ Keywords | schizophrenia |
| 2 | Mol. Biol. Rep. 2013 Aug 40: 5123-8 |
| PMID | 23666060 |
| Title | Evaluation of polymorphism, hypermethylation and expression pattern of CTLA4 gene in a sample of Iranian patients with schizophrenia. |
| Abstract | The cytotoxic T lymphocyte-associated antigen 4 gene (CTLA4) has a crucial role in regulation of T cell proliferation and mediates T cell apoptosis by encoding the T cell receptor.schizophrenia(SCZ) patients often have abnormalities in terms of the function and development of the immune system. The aim of the present study was to investigate promoter variation and expression profile of theCTLA4gene in patients with SCZ. We isolated genomic DNA from peripheral blood of 94 individuals with SCZ and 99 healthy control subjects. Genotypic analysis ofCTLA4(-318) was done by Tetra-ARMS-PCR. Methylation-specific polymerase chain reaction (MS-PCR) was used to estimate promoter hypermethylation of theCTLA4gene. In addition, we investigatedCTLA4mRNA levels in 34 blood samples from cases and healthy controls using real-time reverse transcription PCR. The CT genotype ofCTLA4has a significantly protective effect on the risk to SCZ (OR=0.44; 95% CI 0.18-1.06, P=0.007) in comparison with the wild CC genotype. Promoter methylation of theCTLA4gene increased the risk of disease statistically (OR=3.82, 95% CI 1.34-10.9, P=0.015) in cases when compared to healthy controls in blood samples. The mRNA expression level results showed statistically significant differences (P<0.0001) between cases (n=17) and healthy controls (n=17). To the best of our knowledge, this is the first evidence showing that promoter methylation of theCTLA4gene along with transition of C to T was linked to a significantly higher expression ofCTLA4mRNA levels in patients with SCZ. |
| SCZ Keywords | schizophrenia |
| 3 | Neuropsychobiology 2015 -1 71: 158-67 |
| PMID | 25998553 |
| Title | CTLA4 and CD28 Gene Polymorphisms with Respect to Affective Symptom Domain in Schizophrenia. |
| Abstract | Accumulating evidence indicates that immune alterations inschizophreniaare due to genetic underpinnings. Here, we aimed at investigating whether polymorphisms inCTLA4and CD28 genes, encoding molecules that regulate T-cell activity, influenceschizophreniasymptomatology. We recruited 120schizophrenia患者和380名健康年龄和sex-matched续rols. We divided the patients into two groups: one with no co-occurrence between psychotic and affective symptoms and the second one with psychotic symptoms dominating in the clinical manifestation, although also with occasional affective disturbances in the course of illness. Among the patients with co-occurring affective symptoms, there were significantly moreCTLA4c.49A>G[A] alleles (p = 0.018, odds ratio (OR) 2.03, 95% confidence interval (CI) 1.2-3.66) and moreCTLA4g.319C>T[T] alleles (p = 0.07, OR 1.93, 95% CI 0.94-4.13) in comparison to the second group. Additionally, we have shown that CD28 c.17 + 3T>C[C+] were more significantly overrepresented among patients with co-occurring psychotic and affective symptoms (p = 0.0003, OR 3.36, 95% CI 1.69-6.68) than in patients without co-occurence between these symptoms (p = 0.012, OR 1.88, 95% CI 1.15-3.10). CTLA4and CD28 gene polymorphisms may not only act in immune deregulation observed inschizophrenia, but may also influence the course of the illness by modifying the susceptibility to the co-occurrence of psychotic and affective symptoms. |
| SCZ Keywords | schizophrenia |