Association of Androgen Receptor CAG Repeat Polymorphism and Polycystic Ovary Syndrome
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...
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Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2008-05, Vol.93 (5), p.1939-1945 |
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container_title | The journal of clinical endocrinology and metabolism |
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creator | Shah, Nissar A. Antoine, Heath J. Pall, Marita Taylor, Kent D. Azziz, Ricardo Goodarzi, Mark O. |
description | 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. |
doi_str_mv | 10.1210/jc.2008-0038 |
format | Article |
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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.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/jc.2008-0038</identifier><identifier>PMID: 18303071</identifier><identifier>CODEN: JCEMAZ</identifier><language>eng</language><publisher>Bethesda, MD: Endocrine Society</publisher><subject>Adolescent ; Adult ; Biological and medical sciences ; Endocrinopathies ; Feeding. Feeding behavior ; Female ; Fundamental and applied biological sciences. Psychology ; Humans ; Medical sciences ; Middle Aged ; Original ; Polycystic Ovary Syndrome - genetics ; Polymorphism, Genetic ; Receptors, Androgen - genetics ; Trinucleotide Repeats ; Vertebrates: anatomy and physiology, studies on body, several organs or systems ; Vertebrates: endocrinology ; X Chromosome Inactivation</subject><ispartof>The journal of clinical endocrinology and metabolism, 2008-05, Vol.93 (5), p.1939-1945</ispartof><rights>2008 INIST-CNRS</rights><rights>Copyright © 2008 by The Endocrine Society 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-7b510d6ec6c3abe725fc51567e5136b302a4621e5ebe0b88f36fe9c81530c6c63</citedby><cites>FETCH-LOGICAL-c487t-7b510d6ec6c3abe725fc51567e5136b302a4621e5ebe0b88f36fe9c81530c6c63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20323528$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18303071$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shah, Nissar A.</creatorcontrib><creatorcontrib>Antoine, Heath J.</creatorcontrib><creatorcontrib>Pall, Marita</creatorcontrib><creatorcontrib>Taylor, Kent D.</creatorcontrib><creatorcontrib>Azziz, Ricardo</creatorcontrib><creatorcontrib>Goodarzi, Mark O.</creatorcontrib><title>Association of Androgen Receptor CAG Repeat Polymorphism and Polycystic Ovary Syndrome</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>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.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Endocrinopathies</subject><subject>Feeding. Feeding behavior</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Original</subject><subject>Polycystic Ovary Syndrome - genetics</subject><subject>Polymorphism, Genetic</subject><subject>Receptors, Androgen - genetics</subject><subject>Trinucleotide Repeats</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><subject>Vertebrates: endocrinology</subject><subject>X Chromosome Inactivation</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi0EotvCjTPKBU6kjO34Ixek1QoKUqUivsTNcpxJ61Vip3a20v57ku6qgITEyRr7mdczegh5QeGcMgpvt-6cAegSgOtHZEXrSpSK1uoxWQEwWtaK_TwhpzlvAWhVCf6UnFDNgYOiK_JjnXN03k4-hiJ2xTq0KV5jKL6gw3GKqdisL-ZiRDsVn2O_H2Iab3weChva-wu3z5N3xdWdTfvi637pH_AZedLZPuPz43lGvn94_23zsby8uvi0WV-WrtJqKlUjKLQSnXTcNqiY6JygQioUlMuGA7OVZBQFNgiN1h2XHdZOU8Fh7pH8jLw75I67ZsDWYZiS7c2Y_DCPY6L15u-X4G_MdbwzjGvJ1BLw-hiQ4u0O82QGnx32vQ0Yd9nImtZc8eq_IAOtaiVhBt8cQJdizgm7h2komMWY2TqzGDOLsRl_-ecGv-Gjohl4dQRsdrbvkg3O5weOAWdcsCWIHzgMbXTJBxwT5my2cZfC7ODf3_8Cq46wdQ</recordid><startdate>20080501</startdate><enddate>20080501</enddate><creator>Shah, Nissar A.</creator><creator>Antoine, Heath J.</creator><creator>Pall, Marita</creator><creator>Taylor, Kent D.</creator><creator>Azziz, Ricardo</creator><creator>Goodarzi, Mark O.</creator><general>Endocrine Society</general><general>The Endocrine Society</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20080501</creationdate><title>Association of Androgen Receptor CAG Repeat Polymorphism and Polycystic Ovary Syndrome</title><author>Shah, Nissar A. ; Antoine, Heath J. ; Pall, Marita ; Taylor, Kent D. ; Azziz, Ricardo ; Goodarzi, Mark O.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-7b510d6ec6c3abe725fc51567e5136b302a4621e5ebe0b88f36fe9c81530c6c63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Endocrinopathies</topic><topic>Feeding. Feeding behavior</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Original</topic><topic>Polycystic Ovary Syndrome - genetics</topic><topic>Polymorphism, Genetic</topic><topic>Receptors, Androgen - genetics</topic><topic>Trinucleotide Repeats</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><topic>Vertebrates: endocrinology</topic><topic>X Chromosome Inactivation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shah, Nissar A.</creatorcontrib><creatorcontrib>Antoine, Heath J.</creatorcontrib><creatorcontrib>Pall, Marita</creatorcontrib><creatorcontrib>Taylor, Kent D.</creatorcontrib><creatorcontrib>Azziz, Ricardo</creatorcontrib><creatorcontrib>Goodarzi, Mark O.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shah, Nissar A.</au><au>Antoine, Heath J.</au><au>Pall, Marita</au><au>Taylor, Kent D.</au><au>Azziz, Ricardo</au><au>Goodarzi, Mark O.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of Androgen Receptor CAG Repeat Polymorphism and Polycystic Ovary Syndrome</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2008-05-01</date><risdate>2008</risdate><volume>93</volume><issue>5</issue><spage>1939</spage><epage>1945</epage><pages>1939-1945</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><coden>JCEMAZ</coden><abstract>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.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>18303071</pmid><doi>10.1210/jc.2008-0038</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
subjects | Adolescent Adult Biological and medical sciences Endocrinopathies Feeding. Feeding behavior Female Fundamental and applied biological sciences. Psychology Humans Medical sciences Middle Aged Original Polycystic Ovary Syndrome - genetics Polymorphism, Genetic Receptors, Androgen - genetics Trinucleotide Repeats Vertebrates: anatomy and physiology, studies on body, several organs or systems Vertebrates: endocrinology X Chromosome Inactivation |
title | Association of Androgen Receptor CAG Repeat Polymorphism and Polycystic Ovary Syndrome |
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