title: Exclusion of non-synonymous SNPs and a polyglutamine tract in SMRT/N-CoR2 as common deleterious mutation for bipolar disorder in the Sagnenay-Lac-St-Jean population.
abstract: Bipolar disorder (BP) is a psychiatric illness with both genetic and environmental components occurring with a prevalence of slightly more than 1%. Our previous linkage and case/control studies have pointed to a susceptibility locus for BP in the 12q24.31 chromosomal region. Here, we investigated the possible involvement of the SMRT/N-CoR2 gene, which encodes for the nuclear receptor co-repressor 2. SMRT/N-CoR2 was retained as a candidate gene for BP because of its location within our candidate gene region and its interactions with thyroid hormone receptors. We screened SMRT/N-CoR2 for the presence of polymorphism/mutation in coding sequences and exon-intron junctions. Four non-synonymous SNPs and a polyglutamine tract (CAG repeat) in the coding exon 14 were analyzed in a case/control sample from the Saguenay-Lac-St-Jean (SLSJ) area of Quebec (213 cases and 214 controls). Our data indicated no significant allelic/genotypic association between any of the five mutations and bipolar phenotype when they were considered either individually or as haplotypes. Finally, the CAG repeat observed in SMRT/N-CoR2 did not demonstrate allelic instability and consequently it is unlikely that this polymorphism could be involved in the anticipation phenomenon reported for BP.
authors.affiliation: Neuroscience, CHUL Research Center and Laval University, CHUQ Pavillon CHUL, Ste-Foy, Québec, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Shink
authors.forename: Mario
authors.initials: M
authors.lastname: Harvey
authors.forename: Monique
authors.initials: M
authors.lastname: Tremblay
authors.forename: Catherine
authors.initials: C
authors.lastname: Raymond
authors.forename: Michel
authors.initials: M
authors.lastname: Labbé
authors.forename: Bernard
authors.initials: B
authors.lastname: Gagné
authors.forename: Nicholas
authors.initials: N
authors.lastname: Barden
mesh_terms: D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D005973:Glutamine / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D009154:Mutation; D056985:Nuclear Receptor Co-Repressor 2; D010455:Peptides / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011792:Quebec; D012097:Repressor Proteins / Q000235:genetics*; D018911:Trinucleotide Repeats / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C539130:NCOR2 protein, human; D056985:Nuclear Receptor Co-Repressor 2; D010455:Peptides; D012097:Repressor Proteins; D005973:Glutamine; C097188:polyglutamine