title: Association study of the human partially duplicated alpha7 nicotinic acetylcholine receptor genetic variant with bipolar disorder.
abstract: The human alpha7 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.
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Chen-Jee
authors.initials: CJ
authors.lastname: Hong
authors.forename: I-Ching
authors.initials: IC
authors.lastname: Lai
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Liou
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Tsai
mesh_terms: D000328:Adult; D020029:Base Pairing / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics* / Q000378:metabolism; D001923:Brain Chemistry / Q000235:genetics*; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020131:Genes, Duplicate; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000172:deficiency* / Q000235:genetics; D014029:Tobacco Use Disorder / Q000235:genetics / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579167:Chrna7 protein, human; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine