title: The -2 bp deletion in exon 6 of the 'alpha 7-like' nicotinic receptor subunit gene is a risk factor for the P50 sensory gating deficit.
abstract: Abnormality in the P50 auditory-evoked potential gating is an endophenotype associated with schizophrenia. Biochemical and genetic studies have suggested that the alpha 7 nicotinic acetylcholine receptor (nAChR) is involved in this sensory gating deficit. Two related alpha 7 genes (CHRNA7 and CHRNA7-like gene) resulting from a partial duplication (from exon 5 to exon 10) are present in the human genome. Two types of genetic variation, a large deletion and a -2 base-pair deletion in exon 6 resulting in a truncation of the open reading frame, affect specifically the CHRNA7-like gene. We developed a simple multiplex PCR assay on genomic DNA, allowing the quantification of the number of exons 6 and the distinction of all possible exon 6 genotypes. Genotyping of 70 schizophrenic patients and 77 controls showed that carrying at least one -2 bp deletion of exon 6 did not constitute a risk factor for schizophrenia. In contrast, the distribution of genotypes differed significantly between subjects with normal and abnormal P50 ratios, with an over-representation of genotypes carrying at least one -2 bp deletion of exon 6 among subjects exhibiting an abnormal P50 ratio. We thus conclude that the -2 bp deletion within the CHRNA7-like gene is a risk factor for P50 sensory gating deficit. Interestingly, most of the effect came from the non schizophrenic group, which may suggest that in schizophrenic patients other risk factors account for the large proportion of subjects exhibiting an abnormal P50 ratio.
authors.affiliation: INSERM EMI 9906, IRFMP, Faculté de Medecine et de Pharmacie, Rouen, France.
authors.forename: G
authors.initials: G
authors.lastname: Raux
authors.forename: F
authors.initials: F
authors.lastname: Bonnet-Brilhault
authors.forename: S
authors.initials: S
authors.lastname: Louchart
authors.forename: E
authors.initials: E
authors.lastname: Houy
authors.forename: R
authors.initials: R
authors.lastname: Gantier
authors.forename: D
authors.initials: D
authors.lastname: Levillain
authors.forename: G
authors.initials: G
authors.lastname: Allio
authors.forename: S
authors.initials: S
authors.lastname: Haouzir
authors.forename: M
authors.initials: M
authors.lastname: Petit
authors.forename: M
authors.initials: M
authors.lastname: Martinez
authors.forename: T
authors.initials: T
authors.lastname: Frebourg
authors.forename: F
authors.initials: F
authors.lastname: Thibaut
authors.forename: D
authors.initials: D
authors.lastname: Campion
mesh_terms: D000328:Adult; D005072:Evoked Potentials, Auditory / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011978:Receptors, Nicotinic / Q000235:genetics*; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579167:Chrna7 protein, human; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor