Journal of Neural Transmission

, Volume 114, Issue 4, pp 423–426

Association study of polymorphisms in post-synaptic density protein 95 (PSD-95) with schizophrenia

  • S.-J. Tsai
  • C.-J. Hong
  • C.-Y. Cheng
  • D.-L. Liao
  • Y.-J. Liou
Article

Summary

The postsynaptic density protein 95 (PSD-95) – the prototype of this family – is a modular protein that enables anchoring of NMDA receptors, modulates NMDA receptor sensitivity to glutamate and coordinates NMDA receptor-related intracellular processes. Since hypofunction of NMDA receptors has been implicated in the pathophysiology of schizophrenia, we explored the hypothesis that genetic variants of the PSD-95 gene were associated with a diagnosis of schizophrenia. Three PSD-95 polymorphisms were studied in a sample population of 248 people with schizophrenia and 208 normal controls. One polymorphism (rs373339) was not informative in our Chinese population while the other two polymorphisms (rs2521985 and rs17203281) were analysed with chi-square tests and haplotype analysis. Results demonstrated that the two informative polymorphisms are in strong linkage disequilibrium with each other. Neither single marker nor haplotype analysis revealed an association between variants at the PSD-95 locus and schizophrenia, suggesting that it is unlikely that the PSD-95 polymorphisms investigated play a substantial role in conferring susceptibility to schizophrenia in the Chinese population. Further genetic studies in schizophrenia with other PSD-95-like molecules that interact with the glutamate system are suggested.

Keywords: Association study, polymorphism, postsynaptic density protein 95, schizophrenia, haplotype 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Chumakov, I, Blumenfeld, M, Guerassimenko, O, Cavarec, L, Palicio, M, Abderrahim, H, Bougueleret, L, Barry, C, Tanaka, H, La Rosa, P, Puech, A, Tahri, N, Cohen-Akenine, A, Delabrosse, S, Lissarrague, S, Picard, FP, Maurice, K, Essioux, L, Millasseau, P, Grel, P, Debailleul, V, Simon, AM, Caterina, D, Dufaure, I, Malekzadeh, K, Belova, M, Luan, JJ, Bouillot, M, Sambucy, JL, Primas, G, Saumier, M, Boubkiri, N, Martin-Saumier, S, Nasroune, M, Peixoto, H, Delaye, A, Pinchot, V, Bastucci, M, Guillou, S, Chevillon, M, Sainz-Fuertes, R, Meguenni, S, Aurich-Costa, J, Cherif, D, Gimalac, A, Van Duijn, C, Gauvreau, D, Ouellette, G, Fortier, I, Raelson, J, Sherbatich, T, Riazanskaia, N, Rogaev, E, Raeymaekers, P, Aerssens, J, Konings, F, Luyten, W, Macciardi, F, Sham, PC, Straub, RE, Weinberger, DR, Cohen, N, Cohen, D 2002Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophreniaProc Natl Acad Sci USA991367513680PubMedCrossRefGoogle Scholar
  2. Clinton, SM, Haroutunian, V, Davis, KL, Meador-Woodruff, JH 2003Altered transcript expression of NMDA receptor-associated postsynaptic proteins in the thalamus of subjects with schizophreniaAm J Psychiatry16011001109PubMedCrossRefGoogle Scholar
  3. Dracheva, S, Marras, SA, Elhakem, SL, Kramer, FR, Davis, KL, Haroutunian, V 2001N-methyl-D-aspartic acid receptor expression in the dorsolateral prefrontal cortex of elderly patients with schizophreniaAm J Psychiatry15814001410PubMedCrossRefGoogle Scholar
  4. Dupont, WD, Plummer, WD 1997PS power and sample size program available for free on the InternetControl Clin Trials18274CrossRefGoogle Scholar
  5. Fujii, K, Maeda, K, Hikida, T, Mustafa, AK, Balkissoon, R, Xia, J, Yamada, T, Ozeki, Y, Kawahara, R, Okawa, M, Huganir, RL, Ujike, H, Snyder, SH, Sawa, A 2006Serine racemase binds to PICK1: potential relevance to schizophreniaMol Psychiatry11150157PubMedCrossRefGoogle Scholar
  6. Harrison, PJ, Owen, MJ 2003Genes for schizophrenia? Recent findings and their pathophysiological implicationsLancet361417419PubMedCrossRefGoogle Scholar
  7. Hong, CJ, Liao, DL, Shih, HL, Tsai, SJ 2004Association study of PICK1 rs3952 polymorphism and schizophreniaNeuroreport1519651967PubMedCrossRefGoogle Scholar
  8. Ke, X, Cardon, LR 2003Efficient selective screening of haplotype tag SNPsBioinformatics19287288PubMedCrossRefGoogle Scholar
  9. Kornau, HC, Schenker, LT, Kennedy, MB, Seeburg, PH 1995Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95Science26917371740PubMedCrossRefGoogle Scholar
  10. Laruelle, M, Kegeles, LS, Abi-Dargham, A 2003Glutamate, dopamine, and schizophrenia: from pathophysiology to treatmentAnn N Y Acad Sci1003138158PubMedCrossRefGoogle Scholar
  11. Ohnuma, T, Kato, H, Arai, H, Faull, RL, McKenna, PJ, Emson, PC 2000Gene expression of PSD95 in prefrontal cortex and hippocampus in schizophreniaNeuroreport1131333137PubMedCrossRefGoogle Scholar
  12. Rutter, AR, Stephenson, FA 2000Coexpression of postsynaptic density-95 protein with NMDA receptors results in enhanced receptor expression together with a decreased sensitivity to L-glutamateJ Neurochem7525012510PubMedCrossRefGoogle Scholar
  13. Sheng, M, Pak, DT 2000Ligand-gated ion channel interactions with cytoskeletal and signaling proteinsAnnu Rev Physiol62755778PubMedCrossRefGoogle Scholar
  14. Stefansson, H, Sigurdsson, E, Steinthorsdottir, V, Bjornsdottir, S, Sigmundsson, T, Ghosh, S, Brynjolfsson, J, Gunnarsdottir, S, Ivarsson, O, Chou, TT, Hjaltason, O, Birgisdottir, B, Jonsson, H, Gudnadottir, VG, Gudmundsdottir, E, Bjornsson, A, Ingvarsson, B, Ingason, A, Sigfusson, S, Hardardottir, H, Harvey, RP, Lai, D, Zhou, M, Brunner, D, Mutel, V, Gonzalo, A, Lemke, G, Sainz, J, Johannesson, G, Andresson, T, Gudbjartsson, D, Manolescu, A, Frigge, ML, Gurney, ME, Kong, A, Gulcher, JR, Petursson, H, Stefansson, K 2002Neuregulin 1 and susceptibility to schizophreniaAm J Hum Genet71877892PubMedCrossRefGoogle Scholar
  15. Toro, C, Deakin, JF 2005NMDA receptor subunit NRI and postsynaptic protein PSD-95 in hippocampus and orbitofrontal cortex in schizophrenia and mood disorderSchizophr Res80323330PubMedCrossRefGoogle Scholar
  16. Tsai, SJ, Cheng, CY, Hong, CJ, Liao, DL, Hou, SJ, Yen, FC, Liou, YJ 2006Association study of polymorphisms in glycine transporter with schizophreniaJ Neural Transm11315451549PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • S.-J. Tsai
    • 1
    • 2
  • C.-J. Hong
    • 1
    • 2
  • C.-Y. Cheng
    • 3
    • 4
  • D.-L. Liao
    • 5
    • 7
  • Y.-J. Liou
    • 3
    • 6
    • 7
  1. 1.Department of PsychiatryTaipei Veterans General HospitalTaipeiTaiwan
  2. 2.Division of Psychiatry, School of MedicineNational Yang-Ming UniversityTaipeiTaiwan
  3. 3.Institute of Clinical Medicine, School of MedicineNational Yang-Ming UniversityTaipeiTaiwan
  4. 4.Ching Kuo Institute of Management and HealthKeelungTaiwan
  5. 5.Department of Psychiatry, Executive Yuan Department of HealthPali Psychiatric HospitalTaipeiTaiwan
  6. 6.Department of PsychiatryYuli Veterans HospitalHualienTaiwan
  7. 7.Division of Mental Health and Substance Abuse ResearchNational Health Research InstitutesMiaoliTaiwan

Personalised recommendations