No association of tumor necrosis factor alpha gene polymorphisms with schizophrenia or response to clozapine.

Tumor necrosis factor alpha (TNF-alpha), a potent immunomodulator and proinflammatory cytokine, has been implicated in schizophrenia pathogenesis and clozapine response. Two studies have established an association between schizophrenia and the TNF-alpha gene -308G/A polymorphism; however, both increased and decreased -308A allele frequency have been reported in two analogous investigations. The present study examined the hypothesis that the TNF-alpha gene -308G/A polymorphism confers susceptibility to schizophrenia in 205 patients with schizophrenia compared with 192 controls. A subgroup of 99 clozapine-treated schizophrenia patients was also tested for the genetic effects of this polymorphism, as evidenced by clinical manifestation, and clozapine-related therapeutic outcome and body-weight change. The results of these investigations suggest that the TNF-alpha gene -308G/A variants do not play a major role in susceptibility to, clinical manifestations for, or clozapine response in, schizophrenia.