Abstract
Research has provided strong evidence for oligodendrocyte and myelin-related genes dysfunction in schizophrenia. Several studies have suggested abnormalities in the expression of myelin-related genes including tumor necrosis factor receptor 2 (TNFR2) involved in the neurodegeneration and remyelination. In order to further assess the role of TNFR2 in schizophrenia, we examined a functional bi-allelic polymorphism associated with an impaired NF-KB signaling and cell survival. In the present case/control study, 220 patients with schizophrenia and 176 healthy controls were genotyped by RFLP-PCR for the T/G polymorphism at the position 676 in exon 6 of the TNFR2 gene. We found a trend towards over-representation of TNFR2 676G in the patients compared to the controls (p = 0.19 and 0.09 respectively). Interestingly, when we evaluated the association between this genetic polymorphism and the clinical variables of schizophrenia, our findings indicated that the frequencies of the G/G genotype and the G allele were significantly higher in paranoid (p = 0.014 and p = 0.012 respectively) and adult-onset paranoid (p = 0.004 and p = 0.004 respectively) schizophrenia patient group compared to the controls. The potential association was confirmed by a logistic regression model only for development of the paranoid form of schizophrenia (p = 0.022) indicating a substantially increased risk for paranoid schizophrenia with inheritance of the TNFR2(G) allele. In conclusion, this polymorphism in TNFR2 or a gene in proximity seems to be associated specifically with paranoid schizophrenia, at least in the Tunisian population. A replication of our findings in other and larger populations could be of particular importance to establish TNFR2 as one of the susceptibility genes of paranoid schizophrenia.
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Acknowledgements
We would like to thank the staff of the Department of Psychiatry of the CHU F Bourguiba of Monastir for providing samples and clinical informations. We are grateful to Dr. Souhir Mestiri for critically reading the paper and Mongia Elabed for English revision.
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This work was supported by the Secretary of State of Scientific and Technological Research and the Ministry of Graduated Studies of Scientific and Technological Research.
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Thabet, S., Ben Nejma, M., Zaafrane, F. et al. Association of the Met-196-Arg Variation of Human Tumor Necrosis Factor Receptor 2 (TNFR2) with Paranoid Schizophrenia. J Mol Neurosci 43, 358–363 (2011). https://doi.org/10.1007/s12031-010-9450-x
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DOI: https://doi.org/10.1007/s12031-010-9450-x