Polyglutamine coding genes in bipolar disorder: lack of association with selected candidate loci.
BACKGROUND
Several studies have suggested that expanded trinucleotide repeats, particularly CAG, may have a role in the etiology of BD. Results obtained with the repeat expansion detection technique (RED) have indicated that bipolar patients have an excess of expanded CAG repeats. However, it is not clear which loci account for this difference.


METHODS
Using lithium-responsive bipolar patients in order to reduce heterogeneity, we investigated five 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.


RESULTS
No difference was found in allele distribution between cases and controls for any of the loci studied. In one locus - L10378 - patients had a tendency 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.


CONCLUSIONS
The study has limitations common to most candidate gene association studies, that is, limited number of loci investigated and limited power to detect loci that account for a small proportion of the total genetic variability.


CONCLUSIONS
Our results suggest that the loci investigated have no major role in the genetic predisposition to bipolar disorder.
Turecki
G
G
Centre for Research in Neuroscience, The Montreal General Hospital, McGill University, 1650 Cedar Ave, Montreal, Canada. gustavo@bagel.ipi.mcgill.ca
Alda
M
M
Grof
P
P
Joober
R
R
Lafrenière
R
R
Cavazzoni
P
P
Duffy
A
A
Grof
E
E
Ahrens
B
B
Berghöfer
A
A
Müller-Oerlinghausen
B
B
Dvoráková
M
M
Libigerová
E
E
Vojtechovský
M
M
Zvolský
P
P
Nilsson
A
A
Prochazka
H
H
Licht
R W
RW
Rasmussen
N A
NA
Schou
M
M
Vestergaard
P
P
Holzinger
A
A
Schumann
C
C
Thau
K
K
Rouleau
G A
GA
D000328:Adult; D000368:Aged; D000483:Alleles; D018692:Antimanic Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D002874:Chromosome Mapping; D005260:Female; D005820:Genetic Testing; D006801:Humans; D016651:Lithium Carbonate / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000235:genetics*; D018911:Trinucleotide Repeats / Q000235:genetics
D018692:Antimanic Agents; D010455:Peptides; C097188:polyglutamine; D016651:Lithium Carbonate