title: The glycine transporter 1 gene (GLYT1) is associated with methamphetamine-use disorder.
abstract: Glycine transporter (GlyT)-1 plays a pivotal role in maintaining the glycine level at the glutamatergic synapse. Glycine is an allosteric agonist of N-methyl-D-aspartate (NMDA) receptors. Because activation of NMDA receptors is an essential step for induction of methamphetamine dependence and psychosis, differences in the functioning of GlyT-1 due to genetic variants of the GlyT-1 gene (GLYT1) may influence susceptibility. A case-control genetic association study of the GLYT1 gene examined 204 patients with methamphetamine-use disorder and 210 healthy controls. We examined three single nucleotide polymorphisms (SNPs), SNP1, IVS3 + 411C > T, rs2486001; SNP2, 1056G > A, rs2248829; and SNP3, IVS11 + 22G > A, rs2248632, of the GLYT1 gene and found that SNP1 showed a significant association in both genotype (P = 0.0086) and allele (P = 0.0019) with methamphetamine-use disorder. The T-G haplotype at SNP1 and SNP2 was a significant risk factor for the disorder (P = 0.000039, odds ratio: 2.04). The present findings indicate that genetic variation of the GLYT1 gene may contribute to individual vulnerability to methamphetamine dependence and psychosis.
authors.affiliation: Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 2-5-1 Shikata-cho, Okayama, Japan.
authors.forename: Yukitaka
authors.initials: Y
authors.lastname: Morita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Makiko
authors.initials: M
authors.lastname: Kishimoto
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okahisa
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kotaka
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Harano
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inada
authors.forename: Tokutaro
authors.initials: T
authors.lastname: Komiyama
authors.forename: Toru
authors.initials: T
authors.lastname: Hori
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Yamada
authors.forename: Yoshimoto
authors.initials: Y
authors.lastname: Sekine
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sora
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Kuroda
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D050487:Glycine Plasma Membrane Transport Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011605:Psychoses, Substance-Induced / Q000235:genetics*
chemical_list: D050487:Glycine Plasma Membrane Transport Proteins; C493268:SLC6A9 protein, human; D008694:Methamphetamine