Association between promoter polymorphic haplotypes of interleukin-10 gene and schizophrenia

Background: Schizophrenia is one of the most severe psychiatric disorders, with a worldwide incidence of 1%. Several reports show abnormal cytokine levels in psychotic patients and indicate a possible role of the immune response system in the pathogenesis of schizophrenia. Increased concentrations of interleukin 10 (IL-10) have been found in plasma of schizophrenic patients, suggesting its potential role as a candidate gene for susceptibility to schizophrenia. IL-10 gene maps on chromosome 1 (q31-q32), a locus associated with genetic susceptibility to schizophrenia. Three functional haplotypes of the gene (GCC, ACC, ATA) have been described, derived from different combinations of three "single nucleotide polymorphisms" and directly related to the expression levels of the protein. Methods: We analyzed allele, genotype, and haplotype distributions in an association case-control study involving 106 schizophrenic patients and 143 unrelated healthy volunteers using polymerase chain reaction (PCR)-Single Strand Conformation Polymorphism and PCR Restriction Fragment Length Polymorphism methods. Results: Our results show a significant increase of GCC homozygotes (the high IL-10-producing haplotype) in schizophrenic patients compared to control subjects (χ² = 13, p = .023; odds ratio = 3.03; 95% confidence interval, 1.274-7.355). Conclusions: These data could partly explain the abnormal secretion of IL-10 occurring in schizophrenic patients in response to infections or different stressors and suggest a potential role of IL-10 as a candidate gene for susceptibility to schizophrenia.