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Background  Three  IL-10  gene promoter single nucleotide polymorphisms  -1082G > A, -819C > T  and  -592C > A  and the haplotypes they define in Caucasians,  GCC, ACC, ATA , associated with different IL-10 production rates, have been linked to schizophrenia in some populations with conflicting results. On the basis of the evidence of the sex-dependent effect of certain genes in many complex diseases, we conducted a sex-stratified case-control association study to verify the linkage of the  IL-10  gene promoter SNPs and haplotypes with schizophrenia and the possible sex-specific genetic effect in a Spanish schizophrenic population.    Methods  241 DSM-IV diagnosed Spanish schizophrenic patients and 435 ethnically matched controls were genotyped for  -1082G > A  and  -592C > A  SNPs. Chi squared tests were performed to assess for genetic association of alleles, genotypes and haplotypes with the disease.    Results  The  -1082A  allele (p = 0.027),  A/A  (p = 0.008) and  ATA/ATA  (p = 0.003) genotypes were significantly associated with schizophrenia in females while neither allelic nor genotypic frequencies reached statistical significance in the male population.    Conclusions  Our results highlight the hypothesis of an imbalance towards an inflammatory syndrome as the immune abnormality of schizophrenia. Anyway, a better understanding of the involvement of the immune system would imply the search of immune abnormalities in endophenotypes in whose sex and ethnicity might be differential factors. It also reinforces the need of performing complex gene studies based on multiple cytokine SNPs, including anti and pro-inflammatory, to clarify the immune system abnormalities direction in the etiology of schizophrenia.

ATA homozigosity in the IL-10gene promoter is a risk factor for schizophrenia in Spanish females: a case control study