No association between the Pro197Leu polymorphism in the glutathione peroxidase (GPX1) gene and schizophrenia.
OBJECTIVE
Oxidative stress such as free radical-mediated neuronal dysfunction may be involved in the pathophysiology of schizophrenia. The human glutathione peroxidase (GPX1) is a selenium-dependent enzyme, which plays an important role in the detoxification of free radicals. We therefore hypothesized that the GPX1 gene, which is located on chromosome 3p21.3, may be involved in the pathophysiology of schizophrenia. The aim of this study is to examine whether a potentially functional polymorphism, a proline (Pro) to leucine (Leu) substitution at codon 197 (Pro197Leu) of the human GPX1 gene, is associated with susceptibility to schizophrenia.


METHODS
We genotyped the Pro197Leu polymorphism in a total of 113 nuclear families that had a proband with schizophrenia. Genetic association was tested using the transmission disequilibrium test (TDT), the sib transmission disequilibrium test (STDT), and the family-based association test (FBAT).


RESULTS
The minor allele (Leu) frequency was calculated to be 0.282. We could not find significant transmission disequilibrium of the alleles for the Pro197Leu polymorphism in the GPX1 gene in association with the presence of schizophrenia in our family sample (TDT, chi2=0.03, degrees of freedom=1, P=0.86; combined TDT-STDT, Z'=-0.052, P=0.47; FBAT, Z=0.000, P=1.000).


CONCLUSIONS
The results of this study suggest that the GPX1 polymorphism is unlikely to be associated with susceptibility to schizophrenia.
Neurogenetics Section, Centre for Addiction and Mental Health, Clarke Division, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. takahiro_shinkai@camh.net
Takahiro
T
Shinkai
Vincenzo
V
De Luca
Gwyneth
G
Zai
Sajid
S
Shaikh
Chima
C
Matsumoto
Paul D
PD
Arnold
Rudi
R
Hwang
Nicole
N
King
Joseph
J
Trakalo
Natalia
N
Potapova
Gregory
G
Wong
Hiroko
H
Hori
Albert H C
AH
Wong
Osamu
O
Ohmori
Jun
J
Nakamura
James L
JL
Kennedy
D019943:Amino Acid Substitution; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D005979:Glutathione Peroxidase / Q000235:genetics*; D006801:Humans; D008297:Male; D009679:Nuclear Family; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000201:enzymology / Q000235:genetics*; D000094765:Glutathione Peroxidase GPX1
D017931:DNA Primers; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human