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. (c) 2006 Elsevier Inc. All rights reserved.