The promoter -194 C polymorphism of the nicotinic α7 receptor gene has a protective effect against the P50 sensory gating deficit

INSERM EMI 9906, IFRMP, Faculté de Médecine et de Pharmacie, Rouen, France.
Molecular Psychiatry (Impact Factor: 14.5). 03/2004; 9(3):320-2. DOI: 10.1038/
Source: PubMed


As suggested by several studies, abnormal sensory gating measured by the P50 paradigm could be an endophenotype predisposing to schizophrenia. In a previous work, we have shown a significant association between the presence of at least one -2 bp deletion located within exon 6 of the CHRNA7-like gene and the P50 abnormality in the general population. A recent study involved polymorphisms located in the core promoter region of the CHRNA7 gene as risk factors for the P50 inhibitory deficit. Screening for promoter variants in a large population of schizophrenic patients (n=111) and control subjects (85), for whom auditory-evoked potentials had been recorded did not allow us to replicate these results. By contrast, we showed a significant association between the -194 C allele and a T/C ratio <0.45, thus demonstrating a protective effect of this variant for the sensory gating deficit. Such conflicting results can be reconciled if we consider that the -194 C polymorphism has no causative effect, but is in linkage disequilibrium with other causal variations for the P50 sensory gating deficit, and that different alleles are in disequilibrium in different populations.


Available from: Florence Thibaut, Apr 03, 2014
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    • "Patients with schizophrenia usually show defi cits in both paradigms: PPI (e.g., Aggernaes et al. 2010; Braff et al. 1978), P50 suppression: (e.g., Adler et al. 1982; Boutros et al. 1991; Oranje et al. 2013). There is some evidence indicating that gating defi cits can be ameliorated by among others, nicotine (Adler et al. 1993; Raux et al. 2002; Houy et al, 2004) and α 2a-noradrenergic agonists (Oranje and Glenth ø j 2013, 2014). P50 suppression and PPI defi cits are considered as interesting endophenotypes in schizophrenia. "
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    • "Schizophrenic patients are usually heavy smokers (Dickerson et al., 2013) and smoking is often considered a type of selfmedication which is very much in accordance with deficits in the cholinergic system (Moran et al., 2012). In schizophrenia, the gene for the alpha 7 receptor subunit was found to be related to deficits in sensory gating (Raux et al., 2002; Houy et al., 2004; Martin et al., 2007). In addition, visual acuity was found to be low in CHRNA7 knockout mice (Origlia et al., 2012). "
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    • "In a case–control study, Stephens et al. (2009) detected that rs3087454 ()1831C > A) was significantly associated with schizophrenia . Houy et al. (2004) found that )194G > C in the core promoter region of CHRNA7 was associated with P50 sensory gate deficit. Hong et al. (2004) reported that a )2 bp deletion polymorphism in the duplicated CHRNA7 gene might play a role in the pathogenesis of bipolar disorders patients. "
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