Positive association of the human frizzled 3 (FZD3) gene haplotype with schizophrenia in Chinese Han population.
ABSTRACT Frizzled 3 (FZD3) gene is located on chromosome 8p21, a region that has been implicated in schizophrenia in genetic linkage studies. The FZD3 is a transmembrane receptor required for Wnt signal transduction cascades that have been thought to be involved in producing the cytoarchitectural defects observed in schizophrenia. Previous work has showed a strong association between FZD3 locus and schizophrenia in family-based study. To confirm this issue further, we investigated a genetic association between four single nucleotide polymorphisms (SNPs) located in the FZD3 gene and schizophrenia by case-control study using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) in the Chinese Han population. Our studies showed the SNPs rs2323019 and rs880481 have significant differences in both genotype and allele frequencies between control subjects and schizophrenic patients (rs2323019: Allele A > G, chi2 = 6.7277, df = 1, P = 0.0095; Genotype, chi2 = 10.6583, df = 2, P = 0.0049; rs880481: Allele A > G, chi2 = 10.3945, df = 1, P = 0.0013; Genotype, chi2 = 16.8049, df = 2, P = 0.0002). In addition, we constructed three-locus haplotypes to test their association with schizophrenia. The globe chi-squared test for haplotype analysis showed a significant association (chi2 = 66.38, df = 7, P < 0.000001). These results suggested that the FZD3 gene might be involved in the predisposition to schizophrenia.