Genetic Interaction Between Alpha4 and Beta2 Subunits of High Affinity Nicotinic Receptor: Analysis in Schizophrenia

Overview

Journal Exp Brain Res

Specialty Neurology

Date 2006 Apr 26

PMID 16636791

Citations 23

Authors

Vincenzo De Luca

Sophocles Voineskos

Greg Wong

James L Kennedy

Affiliations

Soon will be listed here.

Abstract

Cholinergic dysfunction is one of the hypotheses for the cognitive deficits of schizophrenia. Neurocognitive deficits, which are well-described clinical features of schizophrenia, may be remediated by nicotine; therefore investigations of nicotinic receptor subtypes is of considerable clinical interest. We typed polymorphisms in CHRNA4 and CHRNB2 genes controlling the expression of neuronal high-affinity nicotinic receptors in 117 Canadian families having at least one schizophrenic patient. Using a family-based association strategy, we performed allele, haplotype and interaction analysis of these two loci. In the families tested, the two cholinergic genes interact to affect schizophrenia in combination (P=0.010), while neither was sufficient alone to confer susceptibility. Our present study provided the first line of direct evidence suggesting that the CHRNA4 gene combined with CHRNB2 receptor gene may be linked to schizophrenia.

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