The glycine transporter 1 gene (GLYT1) is associated with methamphetamine-use disorder.
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.
Morita
Yukitaka
Y
Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 2-5-1 Shikata-cho, Okayama, Japan.
Ujike
Hiroshi
H
Tanaka
Yuji
Y
Kishimoto
Makiko
M
Okahisa
Yuko
Y
Kotaka
Tatsuya
T
Harano
Mutsuo
M
Inada
Toshiya
T
Komiyama
Tokutaro
T
Hori
Toru
T
Yamada
Mitsuhiko
M
Sekine
Yoshimoto
Y
Iwata
Nakao
N
Iyo
Masaomi
M
Sora
Ichiro
I
Ozaki
Norio
N
Kuroda
Shigetoshi
S
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*
D050487:Glycine Plasma Membrane Transport Proteins; C493268:SLC6A9 protein, human; D008694:Methamphetamine