Pro-inflammatory cytokines and their epistatic interactions in genetic susceptibility to schizophrenia

摘要: In schizophrenia, genetic background may provide a substrate for intrinsic maldevelopment of the brain through environmental influences, by recruiting neurotrophic factors and cytokines, to trigger changes that lead impaired neuronal functions. Cytokines being key regulators immune/inflammatory reactions are also known influence dopaminergic, noradrenergic, serotonergic neurotransmission. Therefore, functional polymorphisms in cytokine genes result imbalances pro- anti-inflammatory production. We screened using case-control association study South Indian population. The role allele, genotype, haplotype, diplotypes these their epistatic interactions were assessed contributing risk developing schizophrenia. Meta-analysis reported associations was monitored global significance. pro-inflammatory gene IL1Ars1800587, IL6rs1800796, TNFArs361525, IFNGrs2069718 associated with provides significant evidence strong among IL6 IFNG development silico analysis suggested variants indicative altered transcriptional activity higher production IL1α, IL-6, TNF-α, IFN-ɤ cytokines. indicated heterogeneity population while IL1Ars1800587 found be globally significant. It is important identify nature inflammatory response can amplified environment, either Th1 or Th2 response. involved increased expression resulting cytokines IL-1α, IFN-γ. interaction immunological stressors high producer alleles suggest even lower threshold sufficient induce resultant chronic effect on psycho-social pathogenesis Understanding possibly help dissecting phenotypic variation therapeutic antipsychotics