ATA homozigosity in the IL-10 gene promoter is a risk factor for schizophrenia in Spanish females: a case control study
1 Genetics Department, CAIBER Unit, IIS-Fundacion Jimenez Diaz, Madrid, Spain
2 CIBERER ISCIII, Madrid, Spain
3 Psychiatric Department, IIS - Fundacion Jimenez Diaz, Madrid, Spain
4 CICAB, Clinical Research Centre, CAIBER Unit, Extremadura University Hospital and Medical School, Badajoz, Spain
5 CIBERSAM, ISCIII, Madrid, Spain
6 Clinical Pharmacology Department, CAIBER Unit, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
7 CIBEREHD ISCIII, Madrid, Spain
8 Cancer and Environmental Area, National Center of Epidemiology, ISCIII, Madrid, Spain
9 CIBERESP, ISCIII, Madrid, Spain
10 Psychiatrics Department, Columbia University, New York, USA
11 Department of Cellular Biology and Immunology, CBMSO, CSIC-UAM, Madrid, Spain
12 Department of Preventive Medicine, Public Health and Medical Immunology and Microbiology, School of Health Sciences, Rey Juan Carlos University, Madrid, Spain
BMC Medical Genetics 2011, 12:81 doi:10.1186/1471-2350-12-81Published: 9 June 2011
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.
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.
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.
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.