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Background  Frizzled 3 (Fzd3) is a receptor required for the Wnt-signaling pathway, which has been implicated in the development of the central nervous system, including synaptogenesis and structural plasticity. We previously found a significant association between the  FZD3  gene and susceptibility to schizophrenia, but subsequent studies showed inconsistent findings. To understand the roles of the  FZD3  gene in psychotic disorders further, it should be useful to examine  FZD3  in patients with methamphetamine psychosis because the clinical features of methamphetamine psychosis are similar to those of schizophrenia.    Methods  Six SNPs of  FZD3 , rs3757888 in the 3' flanking region, rs960914 in the intron 3, rs2241802, a synonymous SNP in the exon5, rs2323019 and rs352203 in the intron 5, and rs880481 in the intron 7, were selected based on the previous schizophrenic studies and analyzed in 188 patients with methamphetamine psychosis and 240 age- and gender-matched controls.    Results  A case-control association analyses revealed that two kinds of  FZD3  haplotypes showed strong associations with methamphetamine psychosis ( p  < 0.00001). Having the G-A-T-G or A-G-C-A haplotype of rs2241802-rs2323019-rs352203-rs880481 was a potent negative risk factor (odds ratios were 0.13 and 0.086, respectively) for methamphetamine psychosis.    Conclusion  Our present and previous findings indicate that genetic variants of the  FZD3  gene affect susceptibility to two analogous but distinct dopamine-related psychoses, endogenous and substance-induced psychosis.

The Frizzled 3 gene is associated with methamphetamine psychosis in the Japanese population