Summary.
Glycine acts as an obligatory co-agonist with glutamate on N-methyl-D-aspartate (NMDA) receptors. Brain glycine availability is determined by glycine transporters (GlyT1 or SLC6A9), which mediate glycine reuptake into nerve terminals. Since hypofunction of NMDA receptors has been implicated in the pathophysiology of schizophrenia, this study tests the hypothesis that GlyT1 genetic variants confer susceptibility to schizophrenia. Four GlyT1 polymorphisms were studied in a sample population of 249 people with schizophrenia and 210 normal controls. One polymorphism (rs16831541) was not informative in our Chinese population while the other three polymorphisms (rs1766967, rs2248632 and rs2248253) were analysed with chi-square tests and haplotype analysis. Significant linkage disequilibrium was obtained among the three polymorphisms. Neither single marker nor haplotype analysis revealed an association between variants at the GlyT1 locus and schizophrenia, suggesting that it is unlikely that the GlyT1 polymorphisms investigated play a substantial role in conferring susceptibility to schizophrenia in the Chinese population. Further studies with other GlyT1 variants, relating either to schizophrenia, psychotic symptoms or to therapeutic response in schizophrenia, are suggested.
Similar content being viewed by others
References
JT Coyle G Tsai DC Goff (2002) ArticleTitleIonotropic glutamate receptors as therapeutic targets in schizophrenia Curr Drug Targets CNS Neurol Disord 1 183–189 Occurrence Handle12769626 Occurrence Handle1:CAS:528:DC%2BD38XjvV2nu7w%3D Occurrence Handle10.2174/1568007024606212
CJ Hong DL Liao HL Shih SJ Tsai (2004) ArticleTitleAssociation study of PICK1 rs3952 polymorphism and schizophrenia Neuroreport 15 1965–1967 Occurrence Handle15305146 Occurrence Handle1:CAS:528:DC%2BD2cXmsVCgt7k%3D Occurrence Handle10.1097/00001756-200408260-00026
JW Johnson P Ascher (1987) ArticleTitleGlycine potentiates the NMDA response in cultured mouse brain neurons Nature 325 529–531 Occurrence Handle2433595 Occurrence Handle1:CAS:528:DyaL2sXhtFCju7c%3D Occurrence Handle10.1038/325529a0
EM Jones A Fernald GI Bell MM Le Beau (1995) ArticleTitleAssignment of SLC6A9 to human chromosome band 1p33 by in situ hybridization Cytogenet Cell Genet 71 211 Occurrence Handle7587377 Occurrence Handle1:CAS:528:DyaK28Xhs12ntg%3D%3D Occurrence Handle10.1159/000134110
X Ke LR Cardon (2003) ArticleTitleEfficient selective screening of haplotype tag SNPs Bioinformatics 19 287–288 Occurrence Handle12538253 Occurrence Handle1:CAS:528:DC%2BD3s**tlCnsbs%3D Occurrence Handle10.1093/bioinformatics/19.2.287
KM Kim SF Kingsmore H Han TL Yang-Feng N Godinot MF Seldin MG Caron B Giros (1994) ArticleTitleCloning of the human glycine transporter type 1: molecular and pharmacological characterization of novel isoform variants and chromosomal localization of the gene in the human and mouse genomes Mol Pharmacol 45 608–617 Occurrence Handle8183239 Occurrence Handle1:CAS:528:DyaK2cXkslKms74%3D
JH Krystal LP Karper JP Seibyl GK Freeman R Delaney JD Bremner GR Heninger MB Bowers SuffixJr DS Charney (1994) ArticleTitleSubanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses Arch Gen Psychiatry 51 199–214 Occurrence Handle8122957 Occurrence Handle1:CAS:528:DyaK2cXkslemtrY%3D
JA Lieberman JM Kane J Alvir (1987) ArticleTitleProvocative tests with psychostimulant drugs in schizophrenia Psychopharmacology 91 415–433 Occurrence Handle2884687 Occurrence Handle1:STN:280:BiiB3s3kvVQ%3D Occurrence Handle10.1007/BF00216006
T Lipina V Labrie I Weiner J Roder (2005) ArticleTitleModulators of the glycine site on NMDA receptors, D-serine and ALX 5407, display similar beneficial effects to clozapine in mouse models of schizophrenia Psychopharmacology 179 54–67 Occurrence Handle15759151 Occurrence Handle1:CAS:528:DC%2BD2MXjtV2iurw%3D Occurrence Handle10.1007/s00213-005-2210-x
ED Luby BD Cohen G Rosenbaum JS Gottlieb R Kelley (1959) ArticleTitleStudy of a new schizophrenomimetic drug; sernyl AMA Arch Neurol Psychiatry 81 363–369 Occurrence Handle13626287 Occurrence Handle1:STN:280:CyaD2Mrotlw%3D
G Tsai HY Lane P Yang MY Chong N Lange (2004a) ArticleTitleGlycine transporter I inhibitor, N-methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia Biol Psychiatry 55 452–456 Occurrence Handle1:CAS:528:DC%2BD2c**tFCiur0%3D Occurrence Handle10.1016/j.biopsych.2003.09.012
G Tsai RJ Ralph-Williams M Martina R Bergeron J Berger-Sweeney KS Dunham Z Jiang SB Caine JT Coyle (2004b) ArticleTitleGene knockout of glycine transporter 1: characterization of the behavioral phenotype Proc Natl Acad Sci USA 101 8485–8490 Occurrence Handle1:CAS:528:DC%2BD2cXkvFOmtrc%3D Occurrence Handle10.1073/pnas.0402662101
JB Williams PJ Mallorga P Jeffrey Conn DJ Pettibone C Sur (2004) ArticleTitleEffects of typical and atypical antipsychotics on human glycine transporters Schizophr Res 71 103–112 Occurrence Handle15374578 Occurrence Handle10.1016/j.schres.2004.01.013
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tsai, SJ., Cheng, CY., Hong, CJ. et al. Association study of polymorphisms in glycine transporter with schizophrenia. J Neural Transm 113, 1545–1549 (2006). https://doi.org/10.1007/s00702-006-0438-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00702-006-0438-1