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Zhang C.,Shanghai JiaoTong University | Lu W.,Shanghai JiaoTong University | Ni J.,Tongde Hospital of Zhejiang Province | Zhang J.,Tongde Hospital of Zhejiang Province | And 2 more authors.
Translational Psychiatry | Year: 2016

A novel susceptibility locus (rs11098403) for schizophrenia and bipolar disorder (BD) was identified in an Ashkenazi Jewish population by a recent large-scale genome-wide association study. The rs11098403 is located in the vicinity of the gene encoding N-deacetylase/N-sulfotransferase (heparan glucosaminyl) 3, (NDST3). This study aimed to replicate the results in a Han Chinese population and then potentially extend these findings. We performed a two-stage study to investigate the association of NDST3 with the schizophrenia and BD risk in the Han Chinese. In stage 1, a total of 632 patients with schizophrenia, 654 patients with BD and 684 healthy controls were recruited from the Shanghai region. In stage 2, 522 schizophrenia patients and 547 normal subjects were enrolled from the Hangzhou region. Then, we conducted a meta-analysis based on the present literature. In stage 1, the single nucleotide polymorphism (SNP) rs11098403 showed a significant association with schizophrenia (corrected P=0.005). The frequency of the rs11098403 G allele was significantly lower among schizophrenia patients than among the controls (odds ratio (OR)=0.68, 95% confidence interval (CI): 0.55-0.84, corrected P=0.002). No significant difference was observed in individual SNP marker genotypes or allele distributions between the BD and control groups. In stage 2, the association of rs11098403 with schizophrenia could be validated (genotypic P=0.001 and allelic P=0.0003). After pooling all data from 1861 patients with schizophrenia and 2081 controls, we observed a significant association of the rs11098403 G allele with schizophrenia (Z=5.56, P<0.001), with an OR=0.70 (95% CI: 0.61-0.79). Then, we performed an expression quantitative trait loci analysis to investigate the functional effect of rs11098403 on NDST3 expression in the brain. We observed a significant association of rs11098403 with NDST3 expression in the hippocampus (P=0.027), although the significance did not survive after multiple testing correction. Our findings provided preliminary evidence that rs11098403 might modify the genetic risk of schizophrenia in the Han Chinese. Further investigations are warranted to identify the precise mechanism regulating brain NDST3 expression in the Han Chinese. These results would help to explain the pathophysiological mechanism of schizophrenia. Source


Song M.F.,Hangzhou Seventh Peoples Hospital
Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases | Year: 2013

To investigate the genotoxicity and oxidative stress induced by copper oxide nanoparticles in mice. Thirty mice were randomly divided into control group and low- and high-dose exposure groups. The low- and high-dose exposure groups were given copper oxide nanoparticles (50 and 150 mg/kg) by a single intraperitoneal injection, while the control group was given an equal volume of normal saline containing 0.05%Tween 80. The micronucleus rate of reticulocytes in peripheral blood from the caudal vein and urinary 8-hydroxy-deoxyguanosine (8-OH-dG) level were measured before and at 24, 48, and 72 h after exposure. All the mice were sacrificed at 72 h after exposure, the liver, kidney, and femoral marrow were taken for DNA extraction, and 8-OH-dG in DNA was quantified. The micronucleus rates of peripheral blood reticulocytes in low-dose exposure group at 48 h (3.11±1.46‰ and in high-dose exposure group at 24 and 48 h (4.25±0.43) and 5.42±0.76‰) were significantly increased compared with those before exposure (1.55±0.39‰ and 1.11±0.19‰) and those in control group (1.55±0.28‰ and 1.00±0.67‰) (P < 0.05 or P < 0.01). The urinary 8-OH-dG levels (ng/mg creatinine) in low- and high-dose exposure groups at all time points were significantly increased compared with those before exposure and those in control group (P < 0.05 or P < 0.01). The low- and high-dose exposure groups had significantly higher content of 8-OH-dG in liver DNA than the control group (4.53±1.27 and 7.69±2.78 vs 0.85±0.14, P < 0.01). Copper oxide nanoparticles cause genotoxicity and increase oxidative stress in mice. Source


Tang W.,Hangzhou Seventh Peoples Hospital | Cai J.,Shanghai JiaoTong University | Yi Z.,Shanghai JiaoTong University | Zhang Y.,Shanghai JiaoTong University | And 3 more authors.
Human Psychopharmacology | Year: 2014

In this study, we examined whether common variants in the G protein-coupled receptor kinase 6 gene (GRK6) confers susceptibility to schizophrenia in Chinese. We genotyped two common variants in 697 schizophrenia patients and 563 healthy control subjects. No significant difference in either allele or genotype comparisons between the case and control groups was found. Our results imply that GRK6 may not play a role in the pathophysiology of schizophrenia among Han Chinese. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd. Source


Yang H.-C.,Shenzhen Mental Health Center | Liu T.-B.,Shenzhen Mental Health Center | Rong H.,Shenzhen Mental Health Center | Bi J.-Q.,Shenzhen Mental Health Center | And 15 more authors.
PLoS ONE | Year: 2014

Background: The aim of this study was to test the ability of the Chinese version of the Mood Disorder Questionnaire (MDQ) to identify Bipolar Disorders (BD) in patients diagnosed with Major Depressive Disorder (MDD) or Unipolar Disorder (UD) in the clinical setting. Methods: 1,487 being treated for MDD or UD at 12 mental health centers across China, completed the MDQ and subsequently examined by the Mini International Neuropsychiatric Interview (MINI). Receiver Operating Characteristic(ROC) curves were used to determine the ability of the MDQ to differentiate between BD (BD, BD-I and BD-II) and MDD or UD and patients with BD-I from patients with BD-II. Results: Of the 1,487 patients, 309 (20.8%) satisfied the DSM-IV criteria for BD: 118 (7.9%) for BD-I and 191 (12.8%) for BD-II. When only part one of the MDQ was used, the best cutoff was 7 between BD and UD (sensitivity 0.66, specificity 0.88, positive predictive value 0.59, negative predictive value 0.91), 6 between BD-II and UD, and 10 between BD-I and BD-II. If all three parts of the MDQ were used, the MDQ could not distinguish between BD and UD at a cutoff of 7 (or 6), and the sensitivity was only 0.22 (or 0.24). Conclusion: The Chinese version of the MDQ had good psychometric features in screening bipolar disorders from depressive patients with mood disorders when part two and part three of the MDQ were ignored. © 2014 Yang et al. Source


Chen Z.,Shanghai JiaoTong University | Chen Z.,CAS Kunming Institute of Zoology | Deng-Feng Z.,CAS Kunming Institute of Zoology | Zhi-Guo W.,Shanghai JiaoTong University | And 9 more authors.
British Journal of Psychiatry | Year: 2016

Background: Accumulating evidence suggests that altered immunity contributes to the development of major depressive disorder (MDD). Aims: To examine whether complement factor H (CFH), a regulator of activation of the alternative pathway of the complement cascade, confers susceptibility to MDD. Method: Expression analyses were tested in 53 unmedicated people with MDD and 55 healthy controls. A two-stage genetic association analysis was performed in 3323 Han Chinese with or without MDD. Potential associations between CFH single nucleotide polymorphisms and age at MDD onset were evaluated. Results: CFH levels were significantly lower in the MDD group at both protein and mRNA levels (P = 0.009 and P = 0.014 respectively). A regulatory variant in the CFH gene, rs1061170, showed statistically significant genotypic and allelic differences between the MDD and control groups (genotypic P = 0.0005, allelic P = 0.0001). Kaplan-Meier survival analysis showed that age at onset of MDD was significantly associated with the C allele of rs1061170 (log rank statistic χ2 = 6.82, P = 0.009). The C-allele carriers had a younger age at onset of MDD (22.2 years, s.d. = 4.0) than those without the C allele (23.6 years, s.d. = 4.3). Conclusions: CFH is likely to play an important role in the development of MDD. rs1061170 has an important effect on age at onset of MDD in Han Chinese and may therefore be related to early pathogenesis of MDD, although further study is needed. © The Royal College of Psychiatrists 2016. Source

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