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

Research on -G308A functional polymorphism in the tumor necrosis factor alpha (TNF alpha) 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-cantrol 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 specige when only patients of the paranoid subtype were compared to the controls (relative risk ratio = 3.09, 95% CI = 1.287.47, 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,F-291 = 7.094, p = 0.008). Our results confirm that TNF alpha 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.