Association between Interleukin-10 Gene Promoter Haplotype and Schizophrenia in a Han-Chinese Study

Schizophrenia is a multi-factorial genetic disease, and it is caused by a combination of different gene polymorphisms and not individual ones, however, its pathogenesis is still unclear. The purpose of this study was explored the association between the -1082G/A, -819T/C, and -592C/A polymorphisms of interleukin-10 (IL-10) in schizophrenia. A total of 659 schizophrenics were recruited from a teaching hospital, whereas 411 healthy non-schizophrenic individuals were recruited from community in the same geographical area. The -1082G/A, -819T/C and -592C/A polymorphisms were genotyped by using PCR-RFLP, direct sequencing and TaqMan(®) SNP assay. Both maximum likelihood method of UNPHASED program and Bayesian method of PHASE software were utilized for haplotypic analysis. An allelic frequency difference was found between the schizophrenics and community controls at -1082G/A polymorphism of IL-10 promoter (χ(2) =4.678, P=0.031). A haplotype of ACA was observed to be associated with schizophrenia after performing UNPHASED, PHASE and multivariate logistic regression analysis (P<0.001; P=0.001). In addition, the persons who carry haplotype ACA of IL-10 promoter SNPs were estimated for 5.789 fold higher risk to develop schizophrenia than controls. We postulated this haplotype association might due to variant-specific effect on IL-10 gene regulation, which leads to imbalance secretion of Th(1)/Th(2) cytokines. Nevertheless, more detailed mechanism needs to be elucidated in further investigations in order to confirm this hypothesis.