Allelic variants in the zinc transporter-3 gene,SLC30A3, a candidate gene identified from gene expression studies,show gender-specific association with schizophrenia |
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| Institution: | 1. Neurogenetics Group, Division of Brain Sciences, Faculty of Medicine, Imperial College London, United Kingdom;2. University of Hull and NAViGO, Hull, United Kingdom;3. Benito Menni Complex Assistencial en Salut Mental, Germanes Hospitalàries del Sagrat Cor de Jesús, C/Doctor Antoni Pujades 38-C, 08830 Sant Boi de Llobregat, Barcelona, Spain;1. Institute of Brain, Behaviour and Mental Health, The University of Manchester, Manchester, M13 9PL, United Kingdom;2. Mental Health Unit, Laureate House, Manchester Mental Health & Social Care Trust, Wythenshawe Hospital, Southmoor Road, Manchester, United Kingdom;3. Centre for Biostatistics, Institute of Population Health, The University of Manchester, Manchester, United Kingdom;4. Centre for Mental Health, Imperial College London, Charing Cross Campus, London, United Kingdom;5. Department of Psychiatry & CPFT, University of Cambridge, Cambridge, United Kingdom;1. Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan;2. Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan;3. Yu-Li Veterans Hospital, Yu-Li Town, Hualian County, Taiwan;4. Faculty of Medicine, National Yang Ming University, Taipei, Taiwan;5. Department of Psychiatry, Taichung Veterans General Hospital, Taichung, Taiwan;6. Chung Hwa University of Medical Technology, Tainan, Taiwan;7. Jianan Mental Hospital, Tainan, Taiwan;8. Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung, Taiwan;1. Department of Neurology, Wuqing District Hospital, Tianjin 301700, China;2. Department of Diagnostics, College of Basic Medical Science, Tianjin Medical University, Tianjin, China;1. Institute of Behavioral Medicine, National Cheng Kung University Hospital, Tainan, Taiwan;2. Department of Psychiatry, National Cheng Kung University & Hospital, Tainan, Taiwan;3. Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan;4. Addiction Research Center, National Cheng Kung University, Tainan, Taiwan;5. Department of Psychiatry, Tainan Hospital, Department of Health, Executive Yuan, Tainan, Taiwan;6. Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan;1. Functional Brain Imaging Unit, Wohl Institute for Advanced Imaging, Tel-Aviv Sourasky Medical Center, 6, Weizmann Street, 64239 Tel-Aviv, Israel;2. Psychology Department, Tel-Aviv University, Tel-Aviv, Israel;3. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel;4. Research Unit, Tirat Carmel Mental Health Center, Tirat Carmel, Haifa, Israel;5. Ambulatory Division, Mental health Department, Ramat-Hen, Israel;6. Research Unit, Geha Psychiatric Hospital, Geha, Israel;7. Felsenstein Medical Research Center, Petah Tiqva, Israel;8. Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel |
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| Abstract: | Previous microarray analysis of gene expression in frontal cortex showed differential expression of genes associated with synaptic function in schizophrenia compared to matched-controls in two independent cohorts. One of these genes validated in both cohorts, SLC30A3, which encodes the Zinc Transporter 3 (ZNT3), is localised to synaptic vesicles in glutamate synapses and known to be involved in cognitive function. In view of the robust depletion of SLC30A3 mRNA in two independent studies and the importance of this gene in cognitive function, we investigated whether single nucleotide polymorphism (SNP) associations with schizophrenia could be detected in a UK case controlled schizophrenia cohort. Four SNPs were selected across this gene and genotyped in a cohort of cases and controls from East UK. We found significant associations with schizophrenia at the allelic (ORs: 1.51 to 1.57), genotype (ORs: 1.46 to 1.53) and haplotype level (P = 2.15 × 10−4). These associations proved to be gender-specific with significant effects of allele (ORs: 1.74 to 2.11), genotype (ORs: 1.78 to 2.14) and haplotype (P = 3.51 × 10−5) observed in female schizophrenia cases but not males, when split by gender. In conclusion, SNPs in SLC30A3 showed a gender-specific association with schizophrenia in this East UK cohort, which merits further investigation in other population samples. |
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| Keywords: | Schizophrenia Candidate gene associations Gender effects in schizophrenia Zinc transporter 3 (ZNT3) Synaptic plasticity |
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