The human dihydropyrimidinase-related protein 2 gene on chromosome 8p21 is associated with paranoid-type schizophrenia

Abstract

Backgroud: The dihydropyrimidinase-related protein (DRP) family, also called the collapsin response mediator protein, is implicated in the developmental process of the nervous system. Dysfunction of DRPs may result in neurodevelopmental abnormalities, which may be a factor in the pathogenesis of schizophrenia. The expression of one member of DRP-2 in humans has been reported to be decreased in the brains of people with schizophrenia. In addition, the DRP-2 gene (Dihydropyrimidinaselike 2; DPYSL2) is located on chromosome 8p21, a region that has been implicated in schizophrenia in genetic linkage studies. Methods: We investigated a genetic association between five polymorphisms of the DRP-2 gene and schizophrenia in the Japanese population. Results: The *2236T>C polymorphism in the 3′ untranslated region (3′UTR) exhibited significant differences with respect to the distribution of the genotype and allele in patients compared with control subjects. The frequency of the *2236C allele was significantly higher in control subjects than patients with schizophrenia (p = .0097) and paranoid-type schizophrenia (p = .0083). Conclusions: Our results suggest that the *2236C allele in the 3′UTR of the DRP-2 gene, or an unknown mutation in linkage disequilibrium with this allele, may reduce the susceptibility to schizophrenia, especially the paranoid subtype. © 2003 Society of Biological Psychiatry.