Association of the Met-196-Arg variation of human tumor necrosis factor receptor 2 (TNFR2) with paranoid schizophrenia.

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.

Tumor necrosis factor promoter gene polymorphism associated with increased susceptibility to non-Hodgkin's lymphomas.

The tumor necrosis factor (TNF) is a pro-inflammatory cytokine involved in the severity of different immune-regulated diseases including autoimmune, infectious, and malignant diseases. Chronic immune system stimulation could be a potential etiologic factor in these diseases. Given the determining role of TNF acting early in the immune response, we investigated the effect of an inherited genetic polymorphism at TNF promoter (-308A/G) on a predisposition to non-Hodgkin's lymphoma (NHL). The genotype distribution was determined in 194 patients with NHL and 160 age- and sex-matched population-based controls. The comparison of the -308TNF genotypes between the NHL patients and the controls showed a significant excess of A/A genotype that is previously associated with higher TNF production. Indeed, the A/A genotype is present in 7.7% of the cases, but in only 2.5% of the controls. This genotype is associated with a significant increased risk of NHL (odds ratio = 3.63, P = 0.028). These results indicate that the genetic polymorphism which could lead to an increased TNF production or a neighboring gene within the MHC region may influence the susceptibility to NHL in Tunisian population. Other epidemiologic studies carried out in both the Tunisian population and elsewhere are needed to confirm this finding.