Document Detail


Association of androgen receptor CAG repeat polymorphism and polycystic ovary syndrome.
MedLine Citation:
PMID:  18303071     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT: Genetically determined heightened androgen sensitivity may influence the phenotype of polycystic ovary syndrome (PCOS). To date, studies of the androgen receptor exon 1 polymorphic CAG repeat have produced conflicting results in PCOS.
OBJECTIVE: We tested the hypothesis that a lower number of CAG repeats is associated with increased odds of PCOS. We also compared X-chromosome inactivation between cases and controls.
DESIGN: Women with and without PCOS were genotyped for the CAG repeat and assessed for X-chromosome methylation. Association analyses were performed.
SETTING: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles.
PARTICIPANTS: Participants included 330 women with PCOS and 289 controls (77% white, 23% black).
MAIN MEASUREMENTS: Androgen receptor genotype, X-chromosome methylation, and phenotyping for PCOS were measured.
RESULTS: A smaller biallelic mean of CAG repeats was associated with increased odds of PCOS. X-chromosome inactivation was not different comparing cases with controls; however, in the subset with nonrandom inactivation, the chromosome bearing the shorter CAG allele was preferentially active in PCOS women.
CONCLUSIONS: Association of shorter CAG repeats with PCOS is consistent with in vitro functional studies demonstrating higher activity of androgen receptors expressed from alleles with fewer CAG repeats, suggesting inherited alteration in androgen sensitivity may contribute to PCOS. In some women, such heightened sensitivity may also result from preferential expression of androgen receptors with shorter alleles. Thus, genetic and epigenetic changes may be involved in the pathogenesis of PCOS.
Authors:
Nissar A Shah; Heath J Antoine; Marita Pall; Kent D Taylor; Ricardo Azziz; Mark O Goodarzi
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-02-26
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  93     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-05-08     Completed Date:  2008-06-17     Revised Date:  2013-03-27    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1939-45     Citation Subset:  AIM; IM    
Affiliation:
Division of Endocrinology, Diabetes, and Metabolism, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Female
Humans
Middle Aged
Polycystic Ovary Syndrome / genetics*
Polymorphism, Genetic*
Receptors, Androgen / genetics*
Trinucleotide Repeats*
X Chromosome Inactivation
Grant Support
ID/Acronym/Agency:
K24 HD 01346/HD/NICHD NIH HHS; M01 RR 00425/RR/NCRR NIH HHS; R01 HD 29364/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/AR protein, human; 0/Receptors, Androgen
Comments/Corrections

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