title: Variation in the coding sequence and flanking splice junctions of the estrogen receptor alpha (ERalpha) gene does not play an important role in genetic susceptibility to bipolar disorder or bipolar affective puerperal psychosis.
abstract: Genes involved in estrogen pathways have been proposed as possible candidates influencing susceptibility to bipolar disorder and the affective symptoms suffered by many women during the puerperal period. The estrogen receptor alpha (ERalpha) gene in particular has been a subject of interest and has recently been intensively screened for variations of potential relevance to psychiatric disorders, resulting in the identification of four mutations in individuals with bipolar disorder or puerperal psychosis. We have examined the frequency of these four ERalpha variations in a case control study using a group of mixed gender bipolar individuals (N = 231), further classified into subsets of parous bipolar females with (N = 112) and without (N = 50) puerperal psychosis, and a non-psychiatric comparison group (N = 110). We have also investigated the families in which the variations were initially detected, for evidence of co-segregation of the variants with mood disorder. We found no evidence in our case control sample to support the involvement of any of the ERalpha variations in either the aetiology of bipolar disorder or puerperal triggering of bipolar episodes. Nor did we find co-segregation of ERalpha variants and disease in any of the four families examined. We conclude that variation in the coding sequence and flanking splice junctions of the ERalpha gene does not play an important pathogenic role in the majority of cases of Bipolar Disorder or Bipolar Affective Puerperal Psychosis.
authors.affiliation: Division of Neuroscience, Department of Psychiatry, University of Birmingham, Queen Elizabeth Psychiatric Hospital, Birmingham, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Middle
authors.forename: Ian
authors.initials: I
authors.lastname: Jones
authors.forename: Emma
authors.initials: E
authors.lastname: Robertson
authors.forename: Jaime
authors.initials: J
authors.lastname: Morey
authors.forename: Corinne
authors.initials: C
authors.lastname: Lendon
authors.forename: Nick
authors.initials: N
authors.lastname: Craddock
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D017398:Alternative Splicing / Q000235:genetics*; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D047628:Estrogen Receptor alpha; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D017354:Point Mutation; D011618:Psychotic Disorders / Q000235:genetics*; D011644:Puerperal Disorders / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics*
chemical_list: D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D004247:DNA