MCP-1 gene (SCYA2) and schizophrenia: a case-control association study.

Dysregulation of the inflammatory response system has been linked to the pathophysiology of schizophrenia. Abnormal levels of proinflammatory cytokines and their receptors have been found in peripheral blood and cerebrospinal fluid of schizophrenic patients, suggesting the presence of immune activation. Monocyte chemoattractant protein 1 (MCP-1) influences the expression of cytokines related to T helper responses. MCP-1 also exerts several effects on monocytes, including the expression of several proinflammatory genes. The A-2518G polymorphism of the MCP-1 gene (SCYA2) appears to affect the transcriptional activity and monocyte MCP-1 production. The aim of this case-control study was to investigate the potential role of SCYA2 (A-2518G polymorphism) in conferring susceptibility to schizophrenia and to the resistance to antipsychotic treatment. The sample studied consisted of 191 DSM-IV schizophrenia or schizoaffective disorder (depressive subtype) patients and 161 matched healthy controls. No significant genotypic (chi(2) = 0.278, df = 2, P = 0.986) or allelic (chi(2) = 0.021, df = 1, P = 0.884) association was found between the A-2518G variant of the SCYA2 and the diagnosis. No differences in the age at onset of schizophrenia were found between the three genotype groups identified. Significant genotypic association was found between the A-2518G variant of the SCYA2 and the resistance to antipsychotic treatment (chi(2) = 6.26, df = 2, P = 0.04), with resistant patients more frequently carrying the G allele. The odds ratio associated to the presence of the G allele was 2.39 (95% CI = 1.14-4.98). These data suggest that the A-2518G variant of the SCYA2 has not a major role in the pathogenesis of schizophrenia, while it could be implicated in the resistance to antipsychotic treatment. Copyright 2004 Wiley-Liss, Inc.