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PMID: 17599809 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

Risk for premenstrual dysphoric disorder is associated with genetic variation in ESR1, the estrogen receptor alpha gene.

Biological psychiatry ·Vol. 62 ·No. 8 ·2007-10-15 ·Pages 925-33

Huo L, Straub RE, Roca C, Schmidt PJ, Shi K, Vakkalanka R, Weinberger DR, Rubinow DR

Abstract

Premenstrual dysphoric disorder (PMDD) is a heritable mood disorder that is triggered by gonadal steroids during the luteal phase in susceptible women. We performed haplotype analyses of estrogen receptors alpha and beta (ESR1 and ESR2) in 91 women with prospectively confirmed PMDD and 56 control subjects to investigate possible sources of the genetic susceptibility to affective dysregulation induced by normal levels of gonadal steroids. We also examined associations with the valine (Val)158methionine (Met) single nucleotide polymorphism (SNP) of the gene for catechol-O-methyltransferase (COMT), an enzyme involved in estrogen metabolism and prefrontal cortical activation. Four SNPs in intron 4 of ESR1 showed significantly different genotype and allele distributions between patients and control subjects. Significant case-control differences were seen in sliding-window analyses of two-, three-, and four-marker haplotypes but only in those haplotypes containing SNPs in intron 4 that were positive in the single-locus analysis. No significant associations were observed with ESR2 or with the COMT Val158Met polymorphism, although the significant associations with ESR1 were observed only in those with the Val/Val genotype. These are the first positive (albeit preliminary) genetic findings in this reproductive endocrine-related mood disorder and involve the receptor for a hormone that is pathogenically relevant.

MeSH Terms
Adult Catechol O-Methyltransferase/genetics Chi-Square Distribution Estrogen Receptor alpha/genetics Estrogen Receptor beta/genetics Female Gene Frequency Genetic Predisposition to Disease Haplotypes Humans Linkage Disequilibrium Luteal Phase/genetics,psychology Middle Aged Mood Disorders/complications,genetics Polymorphism, Single Nucleotide Premenstrual Syndrome/complications,genetics
Chemicals
Estrogen Receptor alpha Estrogen Receptor beta Catechol O-Methyltransferase
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Huo Liang
Behavioral Endocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
Straub Richard E
Roca Catherine
Schmidt Peter J
Shi Kai
Vakkalanka Radhakrishna
Weinberger Daniel R
Rubinow David R
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Article Info
Journal
Biological psychiatry
Abbr.
Biol Psychiatry
ISSN
0006-3223
DOI
10.1016/j.biopsych.2006.12.019
Published
2007-10-15
Epub
2007-00-27
Pages
925-33
Language
English
Region
United States
NLM ID
0213264
PMCID
PMC2762203
Subset
IM
Grants
Intramural NIH HHS · Z01 MH002865-02 · United States
External Links
PubMed source DOI: 10.1016/j.biopsych.2006.12.019 PMC Full Text View journal details
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