| 1 | Psychiatry Res 2003 Jun 118: 235-9 |
|---|---|
| PMID | 12834817 |
| Title | NAD(P)H: quinone oxidoreductase (NQO1) gene polymorphism and schizophrenia. |
| Abstract | NAD(P)H: quinone oxidoreductase (NQO1), an obligate two-electron reductase of quinones, prevents their participation in redox cycling and subsequent generation of reactive oxygen species (ROS). Reduced or negative activity of NQO1 would lead to an excess of neurotoxic compounds of cathecolamine o-quinones and ROS. Recently, there has been increasing evidence that catecholamine o-quinones and ROS might contribute to the development of schizophrenia. We investigated the genetic association between a functional polymorphism (Pro 187Ser) in the human NQO1 gene and schizophrenia (244 Japanese schizophrenic patients and 204 healthy controls). No significant differences in the allelic and genotypic distribution between patients and controls were observed. In addition, our results revealed no association between the genotypes of the polymorphism and any characteristics of patients such as gender, age at onset, family history or current neuroleptic dosage. Our results suggest that the NQO1 gene polymorphism does not confer increased susceptibility for schizophrenia in the present sample. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Psychiatr. Genet. 2003 Dec 13: 205-9 |
| PMID | 14639047 |
| Title | A possible association between an insertion/deletion polymorphism of the NQO2 gene and schizophrenia. |
| Abstract | 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. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Psychiatry Res 2003 Jun 118: 235-9 |
| PMID | 12834817 |
| Title | NAD(P)H: quinone oxidoreductase (NQO1) gene polymorphism and schizophrenia. |
| Abstract | NAD(P)H: quinone oxidoreductase (NQO1), an obligate two-electron reductase of quinones, prevents their participation in redox cycling and subsequent generation of reactive oxygen species (ROS). Reduced or negative activity of NQO1 would lead to an excess of neurotoxic compounds of cathecolamine o-quinones and ROS. Recently, there has been increasing evidence that catecholamine o-quinones and ROS might contribute to the development of schizophrenia. We investigated the genetic association between a functional polymorphism (Pro 187Ser) in the human NQO1 gene and schizophrenia (244 Japanese schizophrenic patients and 204 healthy controls). No significant differences in the allelic and genotypic distribution between patients and controls were observed. In addition, our results revealed no association between the genotypes of the polymorphism and any characteristics of patients such as gender, age at onset, family history or current neuroleptic dosage. Our results suggest that the NQO1 gene polymorphism does not confer increased susceptibility for schizophrenia in the present sample. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Psychiatr. Genet. 2003 Dec 13: 205-9 |
| PMID | 14639047 |
| Title | A possible association between an insertion/deletion polymorphism of the NQO2 gene and schizophrenia. |
| Abstract | 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. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Int. J. Neuropsychopharmacol. 2004 Dec 7: 495-500 |
| PMID | 15151706 |
| Title | Quinone oxidoreductase (NQO1) gene polymorphism (609C/T) may be associated with tardive dyskinesia, but not with the development of schizophrenia. |
| Abstract | The association between the quinone oxidoreductase gene (NQO1) polymorphism (609C/T) and schizophrenia was examined to replicate and extend the findings of a previous study (Hori et al., 2003). The study sample was 107 schizophrenia in-patients and 106 healthy controls. The distributions of the NQO1 genotypes and alleles were not different between the schizophrenia patients and the controls. However, the frequency of the variant genotype was significantly higher in the subgroup with tardive dyskinesia (TD) than in the subgroup without (p=0.019). The subjects with allele T were significantly more frequent in the TD patients than in those without (odds ratio 2.256, 95% confidence interval 1.235-4.133). In addition, the Abnormal Involuntary Movement Scale (AIMS) score was significantly higher in the variant genotype group (T/T) than in other genotypic groups (C/C and C/T) (p=0.004). This study suggests that the NQO1 gene polymorphism (609C/T) may confer susceptibility to the development of TD in schizophrenia, at least in the Korean population. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Int. J. Neuropsychopharmacol. 2005 Sep 8: 483-6 |
| PMID | 15836802 |
| Title | Association analysis of NAD(P)Hratioquinone oxidoreductase (NQO1) Pro187Ser genetic polymorphism and tardive dyskinesia in patients with schizophrenia in Taiwan. |
| Abstract | -1 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | Neuromolecular Med. 2006 -1 8: 375-80 |
| PMID | 16775388 |
| Title | No association between a functional NAD(P)H: quinone oxidoreductase gene polymorphism (Pro187Ser) and tardive dyskinesia. |
| Abstract | Several lines of evidence have indicated that free radicals may play a role in the pathophysiology of tardive dyskinesia (TD) (reviewed in Andreassen and Jorgensen, 2000). NAD(P)H: quinone oxidoreductase (NQO1) is an important enzyme in the human body that counteracts the oxidative stress-induced neuronal injury caused by the toxic free radicals such as dopamine-semiquinones. Taking the possible genetic predisposition to TD into account (Yassa and Ananth, 1981), the NQO1 gene is a good candidate gene that may confer increased susceptibility to TD. Based on this hypothesis, Pae et al. (2004) reported a significant association between the Pro187Ser polymorphism in the NQO1 gene and TD. In the present study, we attempted to replicate the findings of Pae et al. (2004) with the same polymorphism in 222 Japanese patients with schizophrenia. No significant difference was detected between patients with and without TD in the allelic distribution (chi2 = 0.070, d.f. = 1, p = 0.795) and in the genotypic distribution (chi2 = 0.910, d.f. = 2, p = 0.657). In addition, there was no significant difference in terms of total Abnormal Involuntary Movement Scale scores among the three genotype groups (p = 0.49). Our results suggest that the NQO1 gene polymorphism does not confer an increased risk of TD. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 8 | Psychiatry Res 2008 Dec 161: 336-8 |
| PMID | 18977034 |
| Title | Additive effect between quinine oxidoreductase gene (NQO1: Pro187Ser) and manganese superoxide dismutase gene (MnSOD: Ala-9Val) polymorphisms on tardive dyskinesia in patients with schizophrenia. |
| Abstract | This study investigated whether there was an interaction between the NQO1 Pro187Ser and MnSOD Ala-9Val gene polymorphisms in the development of tardive dyskinesia (TD). The combined genotypes of T/T in NQO1 Pro187Ser and Val/Val in MnSOD Ala-9Val polymorphisms were found to be independently associated with a significantly higher risk of TD. However, further adequately powered studies will be needed to confirm these preliminary findings. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 9 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2010 Feb 34: 50-6 |
| PMID | 19778569 |
| Title | Oxidative stress in tardive dyskinesia: genetic association study and meta-analysis of NADPH quinine oxidoreductase 1 (NQO1) and Superoxide dismutase 2 (SOD2, MnSOD) genes. |
| Abstract | Tardive dyskinesia (TD) is a potentially irreversible side effect of antipsychotic medication treatment that occurs in approximately 25% of chronically treated schizophrenia patients. Oxidative stress has been one of the proposed mechanisms influencing TD risk. Pae et al. (2004) originally reported a significant association between TD and the NADPH quinine oxidoreductase 1 (NQO1) gene Pro187Ser (C609T, rs1800566) polymorphism in Korean schizophrenia patients; however, subsequent studies have not consistently replicated these findings. Similarly, Hori et al. (2000) reported an association between TD and the Manganese superoxide dismutase SOD2 (MnSOD) gene Ala9Val (rs4880) polymorphism in a Japanese sample, but most research groups failed to replicate their positive findings. We investigated the role of the NQO1 polymorphism Pro187Ser and SOD2 (Ala9Val) in a group of well-characterized schizophrenia patients (N=223) assessed for TD. We also performed a meta-analysis of all the previously published TD studies, including data from our sample, on these polymorphisms, Pro187Ser (N=5 studies) and Ala9Val (N=9 studies). We did not observe a significant association of the Pro187Ser or Ala9Val polymorphism with TD occurrence or AIMS scores in our Caucasian and African American samples when analyzed independently. Meta-analysis did not reveal a significant association of the Pro187Ser/Ala9Val alleles or genotypes with TD occurrence. Neither the NQO1 Pro187Ser nor the SOD2 Ala9Val appear to play a major role in TD risk, although additional polymorphisms should be tested before the role of NQO1 and SOD2 in TD can be completely excluded. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 10 | PLoS ONE 2012 -1 7: e50970 |
| PMID | 23226551 |
| Title | Antipsychotic-induced movement disorders in long-stay psychiatric patients and 45 tag SNPs in 7 candidate genes: a prospective study. |
| Abstract | Four types of antipsychotic-induced movement disorders: tardive dyskinesia (TD), parkinsonism, akathisia and tardive dystonia, subtypes of TD (orofacial and limb truncal dyskinesia), subtypes of parkinsonism (rest tremor, rigidity, and bradykinesia), as well as a principal-factor of the movement disorders and their subtypes, were examined for association with variation in 7 candidate genes (GRIN2B, GRIN2A, HSPG2, DRD3, DRD4, HTR2C, and NQO1). Naturalistic study of 168 white long-stay patients with chronic mental illness requiring long-term antipsychotic treatment, examined by the same rater at least two times over a 4-year period, with a mean follow-up time of 1.1 years, with validated scales for TD, parkinsonism, akathisia, and tardive dystonia. The authors genotyped 45 tag SNPs in 7 candidate genes, associated with movement disorders or schizophrenia in previous studies. Genotype and allele frequency comparisons were performed with multiple regression methods for continuous movement disorders. Various tag SNPs reached nominal significance; TD with rs1345423, rs7192557, rs1650420, as well as rs11644461; orofacial dyskinesia with rs7192557, rs1650420, as well as rs4911871; limb truncal dyskinesia with rs1345423, rs7192557, rs1650420, as well as rs11866328; bradykinesia with rs2192970; akathisia with rs324035; and the principal-factor with rs10772715. After controlling for multiple testing, no significant results remained. The findings suggest that selected tag SNPs are not associated with a susceptibility to movement disorders. However, as the sample size was small and previous studies show inconsistent results, definite conclusions cannot be made. Replication is needed in larger study samples, preferably in longitudinal studies which take the fluctuating course of movement disorders and gene-environment interactions into account. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 11 | Eur. J. Pharmacol. 2012 May 682: 12-20 |
| PMID | 22381068 |
| Title | The sigma-1 receptor protects against cellular oxidative stress and activates antioxidant response elements. |
| Abstract | Sigma-1 receptors are associated with Alzheimer's disease, major depressive disorders, and schizophrenia. These receptors show progrowth/antiapoptotic properties via their chaperoning functions to counteract ER (endoplasmic reticulum) stress, to block neurodegeneration, and to regulate neuritogenesis. The sigma-1 receptor knock out mouse offered an opportunity to assess possible mechanisms by which the sigma-1 receptor modulates cellular oxidative stress. Nuclear magnetic resonance (NMR) metabolomic screening of the WT (wild type) and sigma-1 KO (knockout) livers was performed to investigate major changes in metabolites that are linked to oxidative stress. Significant changes in protein levels were also identified by two-dimensional (2D) gel electrophoresis and mass spectrometry. Increased levels of the antioxidant protein peroxiredoxin 6 (Prdx6), and the ER chaperone BiP (GRP78) compared to WT littermates were detected. Oxidative stress was measured in WT and sigma-1 KO mouse liver homogenates, in primary hepatocytes and in lung homogenates. Furthermore, sigma-1 receptor mediated activation of the antioxidant response element (ARE) to upregulate NAD(P)H quinone oxidoreductase 1 (NQO1) and superoxide dismutase 1 (SOD1) mRNA expression in COS cells was shown by RT PCR. These novel functions of the sigma-1 receptor were sensitive to well-known sigma ligands via their antagonist/agonist properties. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 12 | Arch. Med. Res. 2013 Feb 44: 121-6 |
| PMID | 23360829 |
| Title | Association between polymorphisms in the genes for tumor suppressor protein p53 and its regulator NAD(P)H: quinone oxidoreductase 1 (NQO1) and schizophrenia in a Syrian study cohort. |
| Abstract | The contribution of genetic factors to the susceptibility for developing schizophrenia is well established. Several hypotheses have been developed in an attempt to identify the pathophysiological mechanisms in schizophrenia, with several findings implicating an important role for apoptosis. A limited number of studies investigated the effects of polymorphisms in apoptotic genes on the susceptibility to schizophrenia in different ethnic groups, with none involving an Arab population. The aim of the present study was to investigate the association between multiple polymorphisms in genes for the central apoptotic protein p53 and its regulator NQO1 and the susceptibility for developing schizophrenia in an Arab population from Syria. The studied polymorphisms included exon 4 G>C Arg72Pro (rs1042522), IVS3 16 bp Del/Ins (rs17878362), and MspI IVS6+62A>G (rs1625895) of the TP53 gene, and C609T of the NQO1 gene. The study cohort consisted of 90 patients and 144 healthy controls. Association with each of the four polymorphisms was tested under numerous genetic models. The four polymorphisms were genotyped simultaneously using a quadruplex Tetra-Primer ARMS-PCR method described earlier. The combined effects of polymorphisms in NQO1 and TP53 genes were examined. No statistically significant association was found for any of the four polymorphisms. Our results do not support an association between the studied polymorphisms and schizophrenia in the Syrian population. |
| SCZ Keywords | schizophrenia, schizophrenic |