Glutathione-S-transferases, NAD(P)H: quinone oxidoreductase1 (NQO1) and NRH: quinone oxidoreductase2 (NQO2) provide important cellular defences against the neurotoxicity induced by catecholamine-derived o-quinones and oxidative stress during redox cycling. In this study, we investigated the association between polymorphisms of the NQO2 gene and schizophrenia.
We analysed the promoter and coding regions of the NQO2 gene for 102 patients with schizophrenia and for 234 controls using single-strand conformational change polymorphism and PCR direct-sequencing analyses and the RNA concentration of NQO2 in white blood cells isolated from peripheral blood was measured.
We identified 12 variants including the insertion/deletion (I/D) polymorphism of the 29 base pair nucleotide sequence in the promoter region. The frequency of the D allele was significantly higher in the schizophrenic group than in the control group (P=0.0109). Especially, in patients with the episodic type as course specifiers, this value was highly significant (P=0.0016) and the significance remained after the Bonferroni correction. The 29 base pair nucleotide sequence contains four repeats of the putative core sequence of the Sp1-binding cis-element that is important in the activation of gene expression. Our preliminary data, although sample size was not enough, demonstrated that the RNA concentration of NQO2 in white blood cells isolated from peripheral blood was higher in individuals homozygous (II) for the I allele than in those heterozygous (ID) or homozygous (DD) for the D allele.
The present data suggest that individuals with the deletion of the 29 base pair sequence in the promoter region of the NQO2 gene may confer susceptibility to a certain form of schizophrenia.
aDepartment of Biochemistry, School of Medicine, Keio University, Tokyo, Shinjuku-ku, Japan
bCenter for Molecular Biology and Cytogenetics, SRL, Inc., Hinoshi, Tokyo, Japan
cInstitute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki-ken, Japan
Correspondence and requests for reprints to Shoji Harada, Center for Molecular Biology and Cytogenetics, SRL Inc., Shinmachi 5-6-50, Hinoshi, Tokyo, 191-0002 Japan.
Tel: +81 426 48 3253; fax: +81 426 48 4104;
Received 26 August 2002 Accepted 18 February 2003