title: Allelic variants in the zinc transporter-3 gene, SLC30A3, a candidate gene identified from gene expression studies, show gender-specific association with schizophrenia.
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.
authors.affiliation: Neurogenetics Group, Division of Brain Sciences, Faculty of Medicine, Imperial College London, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Perez-Becerril
authors.affiliation: Neurogenetics Group, Division of Brain Sciences, Faculty of Medicine, Imperial College London, United Kingdom.
authors.forename: A G
authors.initials: AG
authors.lastname: Morris
authors.affiliation: University of Hull and NAViGO, Hull, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Mortimer
authors.affiliation: 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.
authors.forename: P J
authors.initials: PJ
authors.lastname: McKenna
authors.affiliation: Neurogenetics Group, Division of Brain Sciences, Faculty of Medicine, Imperial College London, United Kingdom. Electronic address: j.belleroche@imperial.ac.uk.
authors.forename: J
authors.initials: J
authors.lastname: de Belleroche
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics*; D015331:Cohort Studies; D004739:England / Q000453:epidemiology; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*; D012737:Sex Factors
chemical_list: D027682:Cation Transport Proteins; C102806:SLC30A3 protein, human
keywords: Candidate gene associations; Gender effects in schizophrenia; SLC30A3; Schizophrenia; Synaptic plasticity; Zinc transporter 3 (ZNT3)