Schizophrenia is a multifactorial disease with changes in immunological system. Such changes are the result of cytokine-level disturbances connected with cytokine gene polymorphisms. However, research about cytokine gene polymorphisms in schizophrenia has been surprisingly limited and ambiguous. The aim of the study was to identify whether polymorphisms of interleukin (IL)-6 and IL-10 are risk factors for the development of paranoid schizophrenia in case-control study. IL-6 (-174G/C; rs 1800795) and IL-10 (-1082G/A; rs 1800896) promoter polymorphisms in patients with paranoid schizophrenia and healthy individuals were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Differences in IL-6 and IL-10 promoter haplotypes may play an important role in determining the transcription level for IL-6 and IL-10 genes in schizophrenic patients. The presence of allele C at position -174 of IL-6 promoter sequence may correlate with increasing risk of paranoid schizophrenia in the Polish population, but research on a broadened group of people is needed. The presence of allele G at position -1082 of IL-10 promoter sequence correlates with increasing risk of paranoid schizophrenia in the Polish population. The coexistence of genotype GG at position -1082 of IL-10 promoter sequence and genotype GC at position -174 of IL-6 promoter sequence correlates with increasing risk of paranoid schizophrenia in the Polish population.

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Numerous reports have brought attention to the potential role of cytokines in schizophrenia. The aim of the study was to determine whether polymorphisms of IL-2, IL-6, and TNFα genes are risk factors for development of paranoid schizophrenia in a Polish population. Promoter polymorphisms of IL-6 (rs1800795), TNFα (rs1800629), and IL-2 (rs2069762) genes in patients (N=115) and controls (N=135) were genotyped by PCR-RFLP and AS-PCR methods, respectively. Genotype TT and allele T for IL-2 polymorphism, and genotype AA and allele A for TNFα polymorphism were found to be significantly associated with paranoid schizophrenia. Similarly, haplotypes CTA and GTA increased the risk (4.4 times and 5.9 times, respectively) of schizophrenia. To reveal associations between Positive and Negative Symptom Scale subscales and age at onset of schizophrenia, the authors used a novel method called Grade Correspondence Analysis. This analysis revealed that patients with early age at onset have higher scores on the Negative and General subscales of PANSS, and, in that group of patients, haplotype CTA was the most represented. As far as is known, this analysis was used for the first time with reference to genetic data.

Schizophrenia is a multifactorial disease with changes affecting the immune system. Dysregulation of the cytokine network in schizophrenia has been well documented. Such changes may occur due to disturbances in cytokine levels that are linked to polymorphisms of cytokine genes. However, research in the role of cytokine gene polymorphisms in schizophrenia has been surprisingly scanty. The aim of this study was to identify, in a case control study, whether polymorphism of IFN-γ gene is a risk factor for the development of paranoid schizophrenia. To the best of our knowledge, this is the first study that examines the association between the IFN-γ gene polymorphism and psychopathological symptoms in patients with paranoid schizophrenia. Polymorphism of IFN-γ (+874T/A, rs 62559044) in schizophrenic patients (n=179), as well as healthy individuals (n=196), both Polish residents, was genotyped using AS-PCR method. Of note, when analyzing the results, we took into consideration the gender of studied individuals. Surprisingly, a single-nucleotide polymorphism in the first intron of the IFN-γ gene was found to be associated with paranoid schizophrenia in males, but not in females. The presence of allele A at position +874 in the IFN-γ gene correlates with 1.66-fold higher risk of paranoid schizophrenia development in males. Differences in the genotypes may have an important role in determining the level of I gene transcription. Because other polymorphisms have been demonstrated to influence IFN-γ transcription, further analysis is necessary to clarify the role of this gene in the pathogenesis of paranoid schizophrenia.

The siRNA-induced AKT3 and PI3KCA mRNA knockdown in combination with TMZ and BCNU inhibited proliferation and induced apoptosis and autophagy in T98G cells. Thus, knockdown of these genes in combination with TMZ and BCNU may offer a novel therapeutic strategy to more effectively control the growth of human GBM cells, but further studies are necessary to confirm a positive phenomenon for the treatment of GBM.