Association study of the human partially duplicated α7 nicotinic acetylcholine receptor genetic variant with bipolar disorder

Abstract

The human α7 nicotinic acetylcholine receptor subunit ( CHRNA7) gene cluster maps to the chromosome 15q13-q14 and is implicated as a candidate gene for bipolar disorder (BPD) by genetic linkage study. A −2 bp deletion polymorphism has been found in the duplicated CHRNA7 ( CHRNA7-like) gene, which is located 1 Mb apart from CHRNA7. We tested the hypothesis that the allelic variant, 2 bp deletion (−2 bp), confers susceptibility to BPD or is related to the psychotic features of BPD. We genotyped the −2 bp polymorphism in 77 patients with BPD and 135 normal controls. The distribution of −2 bp genotypes showed a moderately significant difference between the BPD patients and controls ( P=0.044). Three BPD patients carried more than two alleles of the −2 bp deletion genotype, while this genotype was not found in the control group. The −2 bp polymorphism was not associated with age of onset or psychotic features in BPD patients. The results of this study suggest that the −2 bp polymorphism or a nearby polymorphism may play a role in the pathogenesis of BPD. Determination of the functional impact of the −2 bp variant in the nervous system and, in particular, the effect of harboring more than two alleles of the −2 bp deletion needs further exploration.