Polyglutamine coding genes in bipolar disorder: lack of association with selected candidate loci

Background: Several studies have suggested that expanded trinucleotide repe ats, particularly GAG, may have a role in the etiology of ED. Results obtai ned with the repeat expansion detection technique (RED) have indicated that bipolar patients have an excess of expanded CAG repeats. However, it is no t clear which loci account for this difference. Methods: Using lithium-resp onsive bipolar patients in order to reduce heterogeneity, we investigated f ive loci that are expressed in the brain and contain translated CAG repeats . A sample of 138 cases and 108 controls was studied. Genotypes were coded quantitatively or qualitatively and repeat distributions were compared. Res ults: No difference was found in allele distribution between cases and cont rols for any of the loci studied. In one locus - L10378 - patients had a te ndency to present shorter alleles (28.1 versus 27.9 repeats; t = 2.55, df = 205, P = 0.011), however, this difference disappeared after correction for multiple testing. Limitations: The study has limitations common to most ca ndidate gene association studies, that is, limited number of loci investiga ted and limited power to detect loci that account for a small proportion of the total genetic variability. Conclusions: Our results suggest that the l oci investigated have no major role in the genetic predisposition to bipola r disorder. (C) 2000 Elsevier Science BN. All rights reserved.