Significant association of estrogen receptor binding site variation with bipolar disorder in females.

Major depression is nearly twice as prevalent in women compared to men. In bipolar disorder, depressive episodes have been reported to be more common amongst female patients. Furthermore, periods of depression often correlate with periods of hormonal fluctuations. A link between hormone signaling an...

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Main Authors:	Lisette Graae, Robert Karlsson, Silvia Paddock
Format:	article
Language:	EN
Published:	Public Library of Science (PLoS) 2012
Subjects:	Medicine R Science Q
Online Access:	https://doaj.org/article/f5580eaa527745fd9a682e3c746f7ddf
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spelling	oai:doaj.org-article:f5580eaa527745fd9a682e3c746f7ddf2021-11-18T07:26:33ZSignificant association of estrogen receptor binding site variation with bipolar disorder in females.1932-620310.1371/journal.pone.0032304https://doaj.org/article/f5580eaa527745fd9a682e3c746f7ddf2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22389694/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Major depression is nearly twice as prevalent in women compared to men. In bipolar disorder, depressive episodes have been reported to be more common amongst female patients. Furthermore, periods of depression often correlate with periods of hormonal fluctuations. A link between hormone signaling and these mood disorders has, therefore, been suggested to exist in many studies. Estrogen, one of the primary female sex hormones, mediates its effect mostly by binding to estrogen receptors (ERs). Nuclear ERs function as transcription factors and regulate gene transcription by binding to specific DNA sequences. A nucleotide change in the binding sequence might alter the binding efficiency, which could affect transcription levels of nearby genes. In order to investigate if variation in ER DNA-binding sequences may be involved in mood disorders, we conducted a genome-wide study of ER DNA-binding in patients diagnosed with major depression or bipolar disorder. Association studies were performed within each gender separately and the results were corrected for multiple testing by the Bonferroni method. In the female bipolar disorder material a significant association result was found for rs6023059 (corrected p-value = 0.023; odds ratio (OR) 0.681, 95% confidence interval (CI) 0.570-0.814), a single nucleotide polymorphism (SNP) placed downstream of the gene coding for transglutaminase 2 (TGM2). Thus, females with a specific genotype at this SNP may be more vulnerable to fluctuating estrogen levels, which may then act as a triggering factor for bipolar disorder.Lisette GraaeRobert KarlssonSilvia PaddockPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e32304 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lisette Graae Robert Karlsson Silvia Paddock Significant association of estrogen receptor binding site variation with bipolar disorder in females.
description	Major depression is nearly twice as prevalent in women compared to men. In bipolar disorder, depressive episodes have been reported to be more common amongst female patients. Furthermore, periods of depression often correlate with periods of hormonal fluctuations. A link between hormone signaling and these mood disorders has, therefore, been suggested to exist in many studies. Estrogen, one of the primary female sex hormones, mediates its effect mostly by binding to estrogen receptors (ERs). Nuclear ERs function as transcription factors and regulate gene transcription by binding to specific DNA sequences. A nucleotide change in the binding sequence might alter the binding efficiency, which could affect transcription levels of nearby genes. In order to investigate if variation in ER DNA-binding sequences may be involved in mood disorders, we conducted a genome-wide study of ER DNA-binding in patients diagnosed with major depression or bipolar disorder. Association studies were performed within each gender separately and the results were corrected for multiple testing by the Bonferroni method. In the female bipolar disorder material a significant association result was found for rs6023059 (corrected p-value = 0.023; odds ratio (OR) 0.681, 95% confidence interval (CI) 0.570-0.814), a single nucleotide polymorphism (SNP) placed downstream of the gene coding for transglutaminase 2 (TGM2). Thus, females with a specific genotype at this SNP may be more vulnerable to fluctuating estrogen levels, which may then act as a triggering factor for bipolar disorder.
format	article
author	Lisette Graae Robert Karlsson Silvia Paddock
author_facet	Lisette Graae Robert Karlsson Silvia Paddock
author_sort	Lisette Graae
title	Significant association of estrogen receptor binding site variation with bipolar disorder in females.
title_short	Significant association of estrogen receptor binding site variation with bipolar disorder in females.
title_full	Significant association of estrogen receptor binding site variation with bipolar disorder in females.
title_fullStr	Significant association of estrogen receptor binding site variation with bipolar disorder in females.
title_full_unstemmed	Significant association of estrogen receptor binding site variation with bipolar disorder in females.
title_sort	significant association of estrogen receptor binding site variation with bipolar disorder in females.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/f5580eaa527745fd9a682e3c746f7ddf
work_keys_str_mv	AT lisettegraae significantassociationofestrogenreceptorbindingsitevariationwithbipolardisorderinfemales AT robertkarlsson significantassociationofestrogenreceptorbindingsitevariationwithbipolardisorderinfemales AT silviapaddock significantassociationofestrogenreceptorbindingsitevariationwithbipolardisorderinfemales
_version_	1718423510001385472

Significant association of estrogen receptor binding site variation with bipolar disorder in females.

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