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Association study of GSK3 gene polymorphisms with schizophrenia and clozapine response

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Abstract

Rationale

A number of human and animal studies implicate GSK3 in the pathophysiology and genetics of schizophrenia. In general, the data suggest that phosphorylation levels of GSK3β are reduced in schizophrenia, resulting in increased GSK3β activity. Since GSK3β regulation is altered in schizophrenia, polymorphic variation in this gene may affect susceptibility to schizophrenia or treatment response.

Objective

To analyze GSK3β genetic variants for association with schizophrenia and clozapine response.

Materials and methods

We examined GSK3β markers in 185 matched case–control subjects, 85 small nuclear families, and 150 schizophrenia patients treated with clozapine for 6 months.

Results

Three markers (rs7624540, rs4072520, and rs6779828) showed genotypic association with schizophrenia in the case–control sample. We did not observe any family and clozapine response association with a specific allele, genotype, or haplotype.

Conclusions

Our results suggest that GSK3β polymorphisms might be involved in schizophrenia risk but do not appear to play a significant role in clozapine response.

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Acknowledgments

Funding and grants were provided by (1) CNPq—Brazil (#202447/2006-5; #140950/2005-2; #554496/2005-4), (2) National Institutes of Health (NIH), (3) Canadian Institutes of Health Research (CIHR) #940595, (4) Ontario Mental Health Foundation (OMHF), and (5) Fapemig—Brazil. The authors would like to thank Daniela VF Rosa, Mary Smirniw, Nicole King and Arun Tiwari for their help and support throughout the manuscript preparation.

Disclosure/conflicts of interest

Mr. Souza, Dr. Romano-Silva, and Dr. Wong have nothing to declare. Dr. Lieberman has served as a consultant/advisor or grantee of Acadia, Astra Zeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutica, Lundbeck, Merck, Organon, Pfizer, and Wyeth and holds a patent from Repligen. Dr. Meltzer declares that he is a consultant or grantee of Abbott, Acadia, ARYx, Astra Zeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Memory, Minster, Organon, Pfizer, Solvay, Wyeth, and Vanda. Dr. Kennedy declares that he is a consultant for GlaxoSmithKline.

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Authors and Affiliations

  1. Grupo de Pesquisa em Neuropsiquiatria Clínica e Molecular, UFMG, Belo Horizonte, Brazil

    Renan P. Souza & Marco A. Romano-Silva

  2. Saude Mental, UFMG, Belo Horizonte, Brazil

    Renan P. Souza & Marco A. Romano-Silva

  3. Neurogenetics Section, CAMH, Toronto, ON, Canada

    Renan P. Souza, Albert H. C. Wong & James L. Kennedy

  4. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    James L. Kennedy

  5. Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA

    Jeffrey A. Lieberman

  6. Psychiatric Hospital, Vanderbilt University, Nashville, TN, USA

    Herbert Y. Meltzer

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  1. Renan P. Souza
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  2. Marco A. Romano-Silva
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  3. Jeffrey A. Lieberman
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  4. Herbert Y. Meltzer
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  5. Albert H. C. Wong
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  6. James L. Kennedy
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Correspondence to Renan P. Souza.

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Souza, R.P., Romano-Silva, M.A., Lieberman, J.A. et al. Association study of GSK3 gene polymorphisms with schizophrenia and clozapine response. Psychopharmacology 200, 177–186 (2008). https://doi.org/10.1007/s00213-008-1193-9

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  • DOI: https://doi.org/10.1007/s00213-008-1193-9

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