No association between the tumor necrosis factor-alpha gene promoter polymorphisms and schizophrenia in a Japanese population

Tumor necrosis factor-alpha (TNF-α) is a pleiotrophic cytokine and exerts neuroprotective and neurodegenerative effects in brain. Several studies have indicated that TNF-α is likely related to the pathogenesis of schizophrenia. Recent genetic investigations have revealed that a TNF-α gene promoter polymorphism (–G308A) is associated with schizophrenia, although negative findings have also been reported. To assess whether the TNF-α gene promoter variants including –G308A could be implicated in vulnerability to schizophrenia, we conducted a case-control association analysis (265 cases and 424 controls) and the transmission disequilibrium test (TDT) analysis (83 trios) for four polymorphisms (–G238A, –G308A, –C857T and –T1031C) in Japanese subjects. In a case-control analysis, there was no significant association between the promoter polymorphisms or haplotypes in the TNF-α gene and schizophrenia. In the TDT analysis, we also did not observe transmission distortion. Our results suggest that the above four polymorphisms in the promoter region of the TNF-α gene appear not to confer increased susceptibility for schizophrenia in a Japanese population.