Abstract
BackgroundThree 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.Methods241 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.ResultsThe -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.ConclusionsOur 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.
Highlights
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
It is well documented that some cytokines production is regulated at the transcriptional level, which may indicate that the immune alterations in schizophrenia could have a genetic origin [4]. This occurs with IL-10 in which three gene promoter single nucleotide polymorphisms (SNPs), -1082G > A, -819C > T and -592C > A, define three haplotypes in Caucasians, GCC, ACC, ATA, associated to different IL-10 production rates [5]
The aims of this study were to verify the linkage of the IL-10 gene promoter SNPs and haplotypes with schizophrenia and to explore a putative sex-specific genetic association of these polymorphisms in a Spanish schizophrenic population
Summary
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. A key element of this immune theory is the significant increase in the levels of some Th1 (T helper cell type 1) cytokines such as IL-1, IL-6 or TNF (tumor necrosis factor) in plasma, or even cerebrospinal fluid, found in schizophrenic patients, and. This occurs with IL-10 in which three gene promoter single nucleotide polymorphisms (SNPs), -1082G > A, -819C > T and -592C > A, define three haplotypes in Caucasians, GCC, ACC, ATA, associated to different IL-10 production rates [5]. There is evidence of sex-specific association of certain genes with many complex diseases including schizophrenia [8] where sex differences have been described for genes such as RELN [9], XBP1 [10] Nogo [11] and IL-10 [6].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
