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


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.
Souza
Renan P
RP
Grupo de Pesquisa em Neuropsiquiatria Clínica e Molecular, UFMG, Belo Horizonte, Brazil. renanrps@yahoo.com.br
Romano-Silva
Marco A
MA
Lieberman
Jeffrey A
JA
Meltzer
Herbert Y
HY
Wong
Albert H C
AH
Kennedy
James L
JL
D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D003024:Clozapine / Q000627:therapeutic use*; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics*; D000071679:Glycogen Synthase Kinase 3 beta; D006239:Haplotypes; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*
D014150:Antipsychotic Agents; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D003024:Clozapine