-G308A tumor necrosis factor alpha functional polymorphism and schizophrenia risk: Meta-analysis plus association study

Emilio Sacchetti, Luisella Bocchio-Chiavetto, Paolo Valsecchi, Catia Scassellati, Patrizio Pasqualetti, Cristian Bonvicini, Paola Corsini, Giuseppe Rossi, Bruno Mario Cesana, Sergio Barlati, Massimo Gennarelli

Research output: Contribution to journalArticlepeer-review


Research on -G308A functional polymorphism in the tumor necrosis factor α (TNFα) gene as a susceptibility factor for schizophrenia has provided contrasting results in different populations. Therefore we conducted a meta-analysis of the published case-control association studies and a replication study in a large sample. Meta-analyses (total sample: 2512 cases versus 3223 controls) showed that the AA genotype was weakly associated with schizophrenia susceptibility in Caucasoids (Odd Ratio OR = 1.65, 95% CI = 1.00-2.71 Z = 1.98 p = 0.05). The replication case-control association study (323 DSM-IV-TR schizophrenia patients and 346 controls) showed that the A allele conferred an increased susceptibility for schizophrenia only in males (OR = 1.73, 95% CI = 1.07-2.79, p = 0.025), and the association became more specific when only patients of the paranoid subtype were compared to the controls (relative risk ratio = 3.09, 95% CI = 1.28-7.47, p = 0.012). The presence of the A allele was also associated with a later age at onset of schizophrenia in the whole sample (F1,291 = 7.094, p = 0.008). Our results confirm that TNFα A allele could have an effect on vulnerability to schizophrenia but further studies revaluating the role of gender and diagnostic subtypes are necessary to confirm these findings.

Original languageEnglish
Pages (from-to)450-457
Number of pages8
JournalBrain, Behavior, and Immunity
Issue number4
Publication statusPublished - May 2007


  • Age at onset
  • Association
  • Diagnostic subtypes
  • Gender
  • Gene
  • Meta-analysis
  • Paranoid
  • Polymorphism
  • Schizophrenia
  • TNFα

ASJC Scopus subject areas

  • Immunology
  • Behavioral Neuroscience
  • Endocrine and Autonomic Systems


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