Association between-G308A tumor necrosis factor alpha gene polymorphism and schizophrenia

Dysregulation of the inflammatory response system has been linked to pathop hysiology of schizophrenia.(1,2) Evidence of immune activation has derived from the detection of abnormal levels of proinflammatory cytokines and thei r receptors in peripheral blood and cerebrospinal fluid from schizophrenic patients.(3-7) Cytokines are involved in normal CNS development as well as in the pathogenesis of many neuro-psychiatric disorders, acting directly on neural cells or modulating neurotransmitter and neuropeptide systems.(8,9) In particular tumor necrosis factor alpha (TNF alpha), depending on its co ncentration, can exert both neurotrophic and neurotoxic effects and influen ce neural cell growth and proliferation.(10,11) Moreover, TNF alpha gene is located on the small arm of chromosome 6 (6p21.1-21.3), a locus associated with genetic susceptibility to schizophrenia.(12,13) We studied the distri bution of -G308A TNF alpha gene polymorphism in 84 schizophrenic patients a nd in 138 healthy volunteers. This biallelic base exchange polymorphism dir ectly affects TNF alpha plasma levels.(14-18) Frequency of the TNF2(A) alle le is significantly increased in schizophrenic patients as compared to cont rols (P = 0.0042). Genotype distribution is also significantly different (P = 0.0024). TNF2 homozygotes are represented only in the patient group (P = 0.002). These data suggest a potential role of TNF alpha as a candidate ge ne for susceptibility to schizophrenia and suggest that immune dysregulatio n in schizophrenic patients could also have a genetic component.