Association of the Met-196-Arg Variation of Human Tumor Necrosis Factor Receptor 2 (TNFR2) with Paranoid Schizophrenia

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.

Schizophrenia susceptibility and NMDA-receptor mediated signalling: an association study involving 32 tagSNPs of DAO, DAOA, PPP3CC, and DTNBP1genes

“…Similar results were obtained for PPP3CC CAG triplotype carriers and paranoid patients versus schizophrenia as whole (see Additional file 1: Table S3B). Although this putative involvement of DAO and PPP3CC in this specific subgroup was observed also for other genes related to the same glutamatergic/NMDAR regulation [37-40] associated with paranoid schizophrenia, a larger sample is needed to confirm this finding.…”

Symptom clusters of pain, depressed mood, and fatigue in lung cancer: assessing the role of cytokine genes

“…Polymorphisms in TNFR2 have been found to be previously associated with paranoid schizophrenia[40], but to our knowledge, there are no reports describing prior associations with pain, depressed mood or fatigue. Similarly, there have not yet been reports of an association between polymorphisms in the IL10RB gene and pain, depressed mood, or fatigue.…”

Fat-mass and obesity-associated gene polymorphisms and weight gain after risperidone treatment in first episode schizophrenia

“…Schizophrenia is a psychiatric disorder that is associated with impairment in social and occupational functioning [ 1 ]. The use of antipsychotics, especially atypical antipsychotics (AAPs), is associated with serious adverse metabolic effects, including weight gain, hyperlipidemia and glucose intolerance [ 2 ], and other [ 3 ].…”