G72 gene is associated with susceptibility to methamphetamine psychosis.
Methamphetamine psychosis is considered as one of the pharmacological models of schizophrenia, and a hyperdopaminergic one. However, many lines of experimental evidence indicate that glutamatergic signaling is also involved in development of methamphetamine psychosis. Several genes related to glutamate function, e.g. the DTNBP1, G72, and GRM3 genes, were shown to be associated with schizophrenia susceptibility. Recently, we found significant association of the DTNBP1 gene with methamphetamine psychosis. This finding prompted us to examine the G72 gene encoding the d-amino acid oxidase activator (DAOA), which metabolizes d-serine, an NMDA co-agonist, in methamphetamine psychosis. Six SNPs of the G72 gene, which previously showed significant association with schizophrenia, were analyzed in 209 patients with methamphetamine psychosis and 291 age- and sex-matched normal controls. One SNP of M22 (rs778293) showed a significant association with methamphetamine psychosis (genotype: p=0.00016, allele: p=0.0015). Two haplotypes G-A of M12 (rs3916965)-M15 (rs2391191) (p=0.00024) and T-T of M23 (rs947267)-M24 (rs1421292) (p=0.00085) also showed associations with methamphetamine psychosis. The present findings suggest that the G72 gene may contribute to a predisposition to not only schizophrenia but also to methamphetamine psychosis.
Kotaka
Tatsuya
T
Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Ujike
Hiroshi
H
Okahisa
Yuko
Y
Takaki
Manabu
M
Nakata
Kenji
K
Kodama
Masafumi
M
Inada
Toshiya
T
Yamada
Mitsuhiko
M
Uchimura
Naohisa
N
Iwata
Nakao
N
Sora
Ichiro
I
Iyo
Masaomi
M
Ozaki
Norio
N
Kuroda
Shigetoshi
S
D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage* / Q000009:adverse effects*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011605:Psychoses, Substance-Induced / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D011618:Psychotic Disorders / Q000453:epidemiology / Q000235:genetics / Q000523:psychology
D002352:Carrier Proteins; C475071:DAOA protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008694:Methamphetamine