Meta-Analysis of Cytokine and Chemokine Genes in Schizophrenia

Introduction: Immune system genes, including cytokines, are associated with schizophrenia risk. Polymorphisms in cytokine genes may also impact on blood levels of cytokines, which are altered in patients with schizophrenia. We performed a meta-analysis of case-control studies of cytokine and chemokine genes in schizophrenia that have not been considered in previous quantitative reviews.

Methods: We identified articles by systematic searches of PubMed, PsycInfo, and ISI, and the reference lists of identified studies. For each cytokine or chemokine polymorphism, we performed an allele- and genotype-wise meta-analysis, using a random effects model.

Results: Twenty-one independent studies met the inclusion criteria, comprising polymorphisms for the IL1B, IL2, IL4, IL6, sIL6R, MCP1, and TGFB1 genes. For IL6, the A allele (OR=0.95, 95% CI 0.91-0.99) and AA genotype (OR=0.65, 95% CI 0.50-0.85) for the rs1800795 polymorphism, and for sIL6R, the A allele (OR=0.96 95%, CI 0.92-1.00) and AA genotype (OR=0.72, 95% CI 0.55-0.94) the rs8192284 polymorphism were associated with significantly decreased schizophrenia risk. In the genotype-wise analysis for IL1B, homozygosity for either allele (AA: OR=1.91, 95% CI 1.60-2.27; and GG: OR=0.40, 95% CI 0.33-0.49) of the rs1143627 polymorphism was also significantly associated with schizophrenia risk.

Conclusions: Associations between polymorphisms for the IL1B, IL6, and sIL6R genes and schizophrenia risk complement and extend previous findings regarding immune dysfunction in this disorder, including genome-wide association studies. Future studies of cytokine expression in schizophrenia should consider the effect of these polymorphisms. The finding of potential "protective" alleles may also be relevant for at-risk populations.