title: -G308A tumor necrosis factor alpha functional polymorphism and schizophrenia risk: meta-analysis plus association study.
abstract: Research on -G308A functional polymorphism in the tumor necrosis factor alpha (TNFalpha) 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 (F(1,291)=7.094, p=0.008). Our results confirm that TNFalpha 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.
authors.affiliation: Department of Psychiatry, Brescia University School of Medicine, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Sacchetti
authors.forename: Luisella
authors.initials: L
authors.lastname: Bocchio-Chiavetto
authors.forename: Paolo
authors.initials: P
authors.lastname: Valsecchi
authors.forename: Catia
authors.initials: C
authors.lastname: Scassellati
authors.forename: Patrizio
authors.initials: P
authors.lastname: Pasqualetti
authors.forename: Cristian
authors.initials: C
authors.lastname: Bonvicini
authors.forename: Paola
authors.initials: P
authors.lastname: Corsini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rossi
authors.forename: Bruno Mario
authors.initials: BM
authors.lastname: Cesana
authors.forename: Sergio
authors.initials: S
authors.lastname: Barlati
authors.forename: Massimo
authors.initials: M
authors.lastname: Gennarelli
mesh_terms: D000328:Adult; D017668:Age of Onset; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012559:Schizophrenia / Q000145:classification / Q000208:ethnology / Q000235:genetics*; D012737:Sex Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D014409:Tumor Necrosis Factor-alpha