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

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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.

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References

  • I Chumakov M Blumenfeld O Guerassimenko L Cavarec M Palicio H Abderrahim L Bougueleret C Barry H Tanaka P La Rosa A Puech N Tahri A Cohen-Akenine S Delabrosse S Lissarrague FP Picard K Maurice L Essioux P Millasseau P Grel V Debailleul AM Simon D Caterina I Dufaure K Malekzadeh M Belova JJ Luan M Bouillot JL Sambucy G Primas M Saumier N Boubkiri S Martin-Saumier M Nasroune H Peixoto A Delaye V Pinchot M Bastucci S Guillou M Chevillon R Sainz-Fuertes S Meguenni J Aurich-Costa D Cherif A Gimalac C Van Duijn D Gauvreau G Ouellette I Fortier J Raelson T Sherbatich N Riazanskaia E Rogaev P Raeymaekers J Aerssens F Konings W Luyten F Macciardi PC Sham RE Straub DR Weinberger N Cohen D Cohen (2002) ArticleTitleGenetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia Proc Natl Acad Sci USA 99 13675–13680 Occurrence Handle12364586 Occurrence Handle10.1073/pnas.182412499 Occurrence Handle1:CAS:528:DC%2BD38XotVKmtrk%3D

    Article  PubMed  CAS  Google Scholar 

  • SM Clinton V Haroutunian KL Davis JH Meador-Woodruff (2003) ArticleTitleAltered transcript expression of NMDA receptor-associated postsynaptic proteins in the thalamus of subjects with schizophrenia Am J Psychiatry 160 1100–1109 Occurrence Handle12777268 Occurrence Handle10.1176/appi.ajp.160.6.1100

    Article  PubMed  Google Scholar 

  • S Dracheva SA Marras SL Elhakem FR Kramer KL Davis V Haroutunian (2001) ArticleTitleN-methyl-D-aspartic acid receptor expression in the dorsolateral prefrontal cortex of elderly patients with schizophrenia Am J Psychiatry 158 1400–1410 Occurrence Handle11532724 Occurrence Handle10.1176/appi.ajp.158.9.1400 Occurrence Handle1:STN:280:DC%2BD3MvovFKrsw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • WD Dupont WD Plummer (1997) ArticleTitlePS power and sample size program available for free on the Internet Control Clin Trials 18 274 Occurrence Handle10.1016/S0197-2456(97)00074-3

    Article  Google Scholar 

  • K Fujii K Maeda T Hikida AK Mustafa R Balkissoon J Xia T Yamada Y Ozeki R Kawahara M Okawa RL Huganir H Ujike SH Snyder A Sawa (2006) ArticleTitleSerine racemase binds to PICK1: potential relevance to schizophrenia Mol Psychiatry 11 150–157 Occurrence Handle16314870 Occurrence Handle10.1038/sj.mp.4001776 Occurrence Handle1:CAS:528:DC%2BD28XnsV2ltg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • PJ Harrison MJ Owen (2003) ArticleTitleGenes for schizophrenia? Recent findings and their pathophysiological implications Lancet 361 417–419 Occurrence Handle12573388 Occurrence Handle10.1016/S0140-6736(03)12379-3 Occurrence Handle1:CAS:528:DC%2BD3sXptFeisw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • CJ Hong DL Liao HL Shih SJ Tsai (2004) ArticleTitleAssociation study of PICK1 rs3952 polymorphism and schizophrenia Neuroreport 15 1965–1967 Occurrence Handle15305146 Occurrence Handle10.1097/00001756-200408260-00026 Occurrence Handle1:CAS:528:DC%2BD2cXmsVCgt7k%3D

    Article  PubMed  CAS  Google Scholar 

  • X Ke LR Cardon (2003) ArticleTitleEfficient selective screening of haplotype tag SNPs Bioinformatics 19 287–288 Occurrence Handle12538253 Occurrence Handle10.1093/bioinformatics/19.2.287 Occurrence Handle1:CAS:528:DC%2BD3sXitlCnsbs%3D

    Article  PubMed  CAS  Google Scholar 

  • HC Kornau LT Schenker MB Kennedy PH Seeburg (1995) ArticleTitleDomain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95 Science 269 1737–1740 Occurrence Handle7569905 Occurrence Handle10.1126/science.7569905 Occurrence Handle1:CAS:528:DyaK2MXot1aiur0%3D

    Article  PubMed  CAS  Google Scholar 

  • M Laruelle LS Kegeles A Abi-Dargham (2003) ArticleTitleGlutamate, dopamine, and schizophrenia: from pathophysiology to treatment Ann N Y Acad Sci 1003 138–158 Occurrence Handle14684442 Occurrence Handle10.1196/annals.1300.063 Occurrence Handle1:CAS:528:DC%2BD2cXptlGrtg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • T Ohnuma H Kato H Arai RL Faull PJ McKenna PC Emson (2000) ArticleTitleGene expression of PSD95 in prefrontal cortex and hippocampus in schizophrenia Neuroreport 11 3133–3137 Occurrence Handle11043537 Occurrence Handle10.1097/00001756-200009280-00019 Occurrence Handle1:CAS:528:DC%2BD3cXns1Cqt7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • AR Rutter FA Stephenson (2000) ArticleTitleCoexpression of postsynaptic density-95 protein with NMDA receptors results in enhanced receptor expression together with a decreased sensitivity to L-glutamate J Neurochem 75 2501–2510 Occurrence Handle11080203 Occurrence Handle10.1046/j.1471-4159.2000.0752501.x Occurrence Handle1:CAS:528:DC%2BD3cXotFKnsb8%3D

    Article  PubMed  CAS  Google Scholar 

  • M Sheng DT Pak (2000) ArticleTitleLigand-gated ion channel interactions with cytoskeletal and signaling proteins Annu Rev Physiol 62 755–778 Occurrence Handle10845110 Occurrence Handle10.1146/annurev.physiol.62.1.755 Occurrence Handle1:CAS:528:DC%2BD3cXltlGrtrY%3D

    Article  PubMed  CAS  Google Scholar 

  • H Stefansson E Sigurdsson V Steinthorsdottir S Bjornsdottir T Sigmundsson S Ghosh J Brynjolfsson S Gunnarsdottir O Ivarsson TT Chou O Hjaltason B Birgisdottir H Jonsson VG Gudnadottir E Gudmundsdottir A Bjornsson B Ingvarsson A Ingason S Sigfusson H Hardardottir RP Harvey D Lai M Zhou D Brunner V Mutel A Gonzalo G Lemke J Sainz G Johannesson T Andresson D Gudbjartsson A Manolescu ML Frigge ME Gurney A Kong JR Gulcher H Petursson K Stefansson (2002) ArticleTitleNeuregulin 1 and susceptibility to schizophrenia Am J Hum Genet 71 877–892 Occurrence Handle12145742 Occurrence Handle10.1086/342734

    Article  PubMed  Google Scholar 

  • C Toro JF Deakin (2005) ArticleTitleNMDA receptor subunit NRI and postsynaptic protein PSD-95 in hippocampus and orbitofrontal cortex in schizophrenia and mood disorder Schizophr Res 80 323–330 Occurrence Handle16140506 Occurrence Handle10.1016/j.schres.2005.07.003

    Article  PubMed  Google Scholar 

  • SJ Tsai CY Cheng CJ Hong DL Liao SJ Hou FC Yen YJ Liou (2006) ArticleTitleAssociation study of polymorphisms in glycine transporter with schizophrenia J Neural Transm 113 1545–1549 Occurrence Handle16604304 Occurrence Handle10.1007/s00702-006-0438-1 Occurrence Handle1:CAS:528:DC%2BD28XpvVaqsb0%3D

    Article  PubMed  CAS  Google Scholar 

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Tsai, SJ., Hong, CJ., Cheng, CY. et al. Association study of polymorphisms in post-synaptic density protein 95 (PSD-95) with schizophrenia. J Neural Transm 114, 423–426 (2007). https://doi.org/10.1007/s00702-006-0587-2

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  • DOI: https://doi.org/10.1007/s00702-006-0587-2

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