Variation in the coding sequence and flanking splice junctions of the estrogen receptor alpha (ERα) gene does not play an important role in genetic susceptibility to bipolar disorder or bipolar affective puerperal psychosis

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Vol. 118B; no. 1; pp. 72 - 75
• Main Authors: Middle, Fiona, Jones, Ian, Robertson, Emma, Morey, Jaime, Lendon, Corinne, Craddock, Nick
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 01.04.2003
• Subjects: Adult; Aged; Alleles; Alternative Splicing - genetics; association study; bipolar disorder; Bipolar Disorder - genetics; Case-Control Studies; DNA - genetics; Estrogen Receptor alpha; estrogen receptors; Female; gene; Gene Frequency; Genetic Variation; Genotype; Humans; Male; Middle Aged; Mutation, Missense; Point Mutation; Psychotic Disorders - genetics; Puerperal Disorders - genetics; puerperal psychosis; Receptors, Estrogen - genetics
• ISSN: 1552-4841; 1552-485X
• DOI: 10.1002/ajmg.b.10021

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 (ERα) 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 ERα 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 ERα variations in either the aetiology of bipolar disorder or puerperal triggering of bipolar episodes. Nor did we find co‐segregation of ERα variants and disease in any of the four families examined. We conclude that variation in the coding sequence and flanking splice junctions of the ERα gene does not play an important pathogenic role in the majority of cases of Bipolar Disorder or Bipolar Affective Puerperal Psychosis. © 2003 Wiley‐Liss, Inc.