Tumor necrosis factor-alpha −G308A polymorphism in schizophrenia in a Finnish population

Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine with functions in nerve cell growth, differentiation, and apoptosis. There are several studies showing that a TNF-α −G308A promoter polymorphism, which possibly affects TNF-α transcription, is associated with schizophrenia, although negative results also exist. Our aim was to investigate the relationship between the TNF-α −G308A promoter polymorphism, the risk of schizophrenia, and the age of onset of schizophrenia, and the TNF-α −G308A polymorphism was therefore studied in 149 southern Finnish patients with a DSM-IV diagnosis of schizophrenia and in 393 healthy controls. The allele and genotype frequencies did not differ significantly between the patient and control groups (P = 0.10 and 0.12, respectively), but the frequency of G/G homozygotes was statistically significantly higher in male patients than in male controls (χ2 = 5.03, d.f. = 1, P = 0.025) with an odds ratio of 2.00 (95% confidence interval: 1.08-3.70). No such difference was seen in female patients (P = 0.79) or in the whole study group (P = 0.064). The age of onset of schizophrenia did not differ significantly between the different TNF-α genotypes (ANOVA: F = 0.45, P = 0.64). In conclusion, we did not find a clear association between the TNF-α −G308A polymorphism and schizophrenia in the whole study group. However, TNF-α −G308A G/G homozygosity was modestly associated with schizophrenia in male patients.