Association study of the human partially duplicated alpha7 nicotinic acetylcholine receptor genetic variant with bipolar disorder.
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.
Hong
Chen-Jee
CJ
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
Lai
I-Ching
IC
Liou
Ling-Ling
LL
Tsai
Shih-Jen
SJ
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
C579167:Chrna7 protein, human; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine