Association study of the human partially duplicated alpha7 nicotinic acetylcholine receptor genetic variant with bipolar disorder

Neurosci Lett. 2004 Jan 23;355(1-2):69-72. doi: 10.1016/j.neulet.2003.10.043.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Pairing / genetics
  • Bipolar Disorder / genetics*
  • Bipolar Disorder / metabolism
  • Brain Chemistry / genetics*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 15 / genetics
  • DNA Mutational Analysis
  • Female
  • Gene Frequency / genetics
  • Genes, Duplicate
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Genetic Variation / genetics
  • Genotype
  • Humans
  • Male
  • Nicotine / pharmacology
  • Point Mutation / genetics
  • Polymorphism, Genetic / genetics*
  • Receptors, Nicotinic / deficiency*
  • Receptors, Nicotinic / genetics
  • Tobacco Use Disorder / genetics
  • Tobacco Use Disorder / metabolism
  • alpha7 Nicotinic Acetylcholine Receptor


  • Chrna7 protein, human
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor
  • Nicotine