title: Study on GRIA2, GRIA3 and GRIA4 genes highlights a positive association between schizophrenia and GRIA3 in female patients.
abstract: Impairment of glutamatergic neurotransmission is one of the major hypotheses proposed to explain the neurobiology of schizophrenia. Therefore, the genes involved in the glutamate neurotransmitter system could be considered potential candidate genes for schizophrenia susceptibility. A systematic study on alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor genes has been carried out and the results obtained from the analysis on GRIA2, GRIA3 and GRIA4 are reported. No evidence of association with schizophrenia was found for the GRIA2 and GRIA4 genes; strong evidence of association with schizophrenia was found for GRIA3. This X-linked gene showed a different behavior in the two genders; a positive association with schizophrenia was observed among females but not in males. Female carriers of rs1034428 A allele were found to have a 2.19-fold higher risk of developing schizophrenia compared to non-carriers and 3.28-fold higher risk for developing a non-paranoid phenotype. The analysis at the haplotype level showed that susceptibility to schizophrenia was associated with the specific haplotype rs989638-rs1034428-rs2227098 CAC (P = 0.0008). We conclude that, of the three AMPA genes analyzed here, only GRIA3 seems to be involved in the pathogenesis of schizophrenia, but only in females.
authors.affiliation: Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnology, Brescia University School of Medicine, Viale Europa, Brescia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Magri
authors.forename: Rita
authors.initials: R
authors.lastname: Gardella
authors.forename: Paolo
authors.initials: P
authors.lastname: Valsecchi
authors.forename: Stefano Davide
authors.initials: SD
authors.lastname: Barlati
authors.forename: Luca
authors.initials: L
authors.lastname: Guizzetti
authors.forename: Laura
authors.initials: L
authors.lastname: Imperadori
authors.forename: Cristian
authors.initials: C
authors.lastname: Bonvicini
authors.forename: Gian Battista
authors.initials: GB
authors.lastname: Tura
authors.forename: Massimo
authors.initials: M
authors.lastname: Gennarelli
authors.forename: Emilio
authors.initials: E
authors.lastname: Sacchetti
authors.forename: Sergio
authors.initials: S
authors.lastname: Barlati
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D018091:Receptors, AMPA / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D012727:Sex Characteristics
chemical_list: D018091:Receptors, AMPA; C104723:glutamate receptor ionotropic, AMPA 3; C104724:glutamate receptor ionotropic, AMPA 4; C104722:glutamate receptor ionotropic, AMPA 2