title: The T393C polymorphism of the GNAS1 gene is associated with deficit schizophrenia in an Italian population sample.
abstract: Programmed cell death and alterations in intracellular G-protein signaling may be involved in the pathophysiology of schizophrenia. The Galphas subunit of heterotrimeric G-proteins, encoded by the gene GNAS1, may play a role in both of these processes. Additionally, transgenic mice expressing a constitutively active form of Galphas provide a reliable model of certain endophenotypes of schizophrenia. To investigate whether the functional single nucleotide polymorphism T393C in GNAS1 gene could affect risk of schizophrenia, we examined its distribution in Italian subjects with (n=383) and without (n=400) schizophrenia. We also evaluated whether a specific association could exist between the deficit (n=108) and nondeficit (n=275) forms of the disorder. The alleles and genotypes frequency in the entire cohort of schizophrenic patients did not differ from that of controls. However, the frequency of the homozygous 393TT genotype was significantly higher in deficit schizophrenic patients (37.1%) compared to both nondeficit schizophrenic (22.5%, p=0.011) and controls (22.8%, p=0.015). This association with deficit schizophrenia persisted even after allowance for potential confounders [adjusted odds ratio (OR) for deficit schizophrenia: 2.06 (95% confidence interval (CI): 1.21-3.47), p=0.007]. Altogether, our data suggest that the GNAS1 T393C status could influence susceptibility for deficit schizophrenia in Italian subjects.
authors.affiliation: Interdepartmental Center for Research in Molecular Medicine (CIRMC), University of Pavia, Viale Taramelli 24, I-27100 Pavia, Italy.
authors.forename: Piercarlo
authors.initials: P
authors.lastname: Minoretti
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Politi
authors.forename: Enrico
authors.initials: E
authors.lastname: Coen
authors.forename: Clara
authors.initials: C
authors.lastname: Di Vito
authors.forename: Marco
authors.initials: M
authors.lastname: Bertona
authors.forename: Marika
authors.initials: M
authors.lastname: Bianchi
authors.forename: Enzo
authors.initials: E
authors.lastname: Emanuele
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002864:Chromogranins; D003430:Cross-Sectional Studies; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012559:Schizophrenia / Q000145:classification / Q000235:genetics*; D012565:Schizophrenic Psychology; D018709:Statistics, Nonparametric
chemical_list: D002864:Chromogranins; D012333:RNA, Messenger; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs