Association study of GSK3 gene polymorphisms with schizophrenia and clozapine response.

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 GSK3beta are reduced in schizophrenia, resulting in increased GSK3beta activity. Since GSK3beta regulation is altered in schizophrenia, polymorphic variation in this gene may affect susceptibility to schizophrenia or treatment response.

OBJECTIVE:

To analyze GSK3beta genetic variants for association with schizophrenia and clozapine response.

MATERIALS AND METHODS:

We examined GSK3beta 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 GSK3beta polymorphisms might be involved in schizophrenia risk but do not appear to play a significant role in clozapine response.

• Authors: Renan P Souza, Marco A Romano-Silva, Jeffrey A Lieberman, Herbert Y Meltzer, Albert H C Wong, James L Kennedy
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 200 Issue 2 Pg. 177-86 (Oct 2008) ISSN: 0033-3158 [Print] Germany
• PMID: 18500637 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antipsychotic Agents
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• Glycogen Synthase Kinase 3
• Clozapine

Topics

• Adult
• Alleles
• Antipsychotic Agents (therapeutic use)
• Case-Control Studies
• Clozapine (therapeutic use)
• Family
• Female
• Genetic Predisposition to Disease
• Glycogen Synthase Kinase 3 (genetics)
• Glycogen Synthase Kinase 3 beta
• Haplotypes
• Humans
• Male
• Polymorphism, Genetic
• Schizophrenia (drug therapy, genetics)