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The promoter −194 C polymorphism of the nicotinic alpha 7 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: 15.15). 03/2004; 9(3):320-2. DOI: 10.1038/sj.mp.4001443
Source: PubMed

ABSTRACT 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.

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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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    • "Exons 1–6 correspond to the receptor's extracellular N-terminal region containing the ligand binding domain; exons 7 and 8 correspond to the first three transmembrane regions, the second of which constitutes the receptor's ion channel (Changeux et al., 1998); and exons 9 and 10 encode its intracellular cytoplasmic loop and fourth transmembrane region. The gene is located on chromosome 15 and maps to position 15q13-q14 (a locus linked to schizophrenia) and α7 is involved in the P50 sensory gating deficit characterising schizophrenic patients, which is normalised by nicotine (Houy et al., 2004; Leonard et al., 2000, 2002). "
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