Association between the Regulator of G-protein Signaling 9 Gene and Patients with Methamphetamine Use Disorder and Schizophrenia

Y.      Okahisa; M.      Kodama; M.      Takaki; T.      Inada; N.      Uchimura; M.      Yamada; N.      Iwata; M.      Iyo; I.      Sora; N.      Ozaki; H.      Ujike

Abstract

The regulator of G-protein signaling (RGS) modulates the functioning of heterotrimeric G protein. RGS9-2 is highly expressed in the striatum and plays a role in modulating dopaminergic receptor-mediated signaling cascades. Previous studies suggested that the RGS9 gene might contribute to the susceptibility to psychotic diseases. Therefore, we investigated the association between the RGS9 gene and two related dopamine psychoses, schizophrenia and methamphetamine use disorders. The subjects comprised 487 patients of schizophrenia and 464 age- and sex-matched healthy controls and 220 patients of methamphetamine use disorder and 289 controls. We genotyped two nonsynonymous polymorphisms, rs12452285 (Leu225Ser) and rs34797451 (His498Arg), of the RGS9 gene. Rs34797451 showed monomorphism in the present Japanese population, but rs12452285 showed polymorphism. There were no significant differences in genotypic or allelic distributions of rs12452285 between patients with schizophrenia and the corresponding control or between patients with methamphetamine use disorder and the corresponding control. We also analyzed the clinical features of methamphetamine use disorder. We found a significant association in allelic distribution with the phenotypes of age at first consumption (p=0.047). The present study suggested that the RGS9 gene is unlikely to play a major role in schizophrenia and methamphetamine dependence liability and/or the development of methamphetamine induced psychosis, at least in a Japanese population.

Keywords: Substance abuse, methamphetamine, regulator of G-protein signaling 9, case-control association, cocaine, opioids, cannabinoids, alcohol, nicotine, schizophrenia, psychiatric disorders, G-protein signaling (RGS)