Variants in the 5alpha-reductase type 1 and type 2 genes are associated with polycystic ovary syndrome and the severity of hirsutism in affected women
Despite the importance of dihydrotestosterone in androgen action, polymorphisms in the genes for the two isoforms of 5alpha-reductase (SRD5A1 and SRD5A2) have not been evaluated as risk factors for polycystic ovary syndrome (PCOS). The objective of the study was to test the hypothesis that haplotype...
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Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2006-10, Vol.91 (10), p.4085-4091 |
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creator | Goodarzi, Mark O Shah, Nissar A Antoine, Heath J Pall, Marita Guo, Xiuqing Azziz, Ricardo |
description | Despite the importance of dihydrotestosterone in androgen action, polymorphisms in the genes for the two isoforms of 5alpha-reductase (SRD5A1 and SRD5A2) have not been evaluated as risk factors for polycystic ovary syndrome (PCOS).
The objective of the study was to test the hypothesis that haplotypes in the SRD5A1 and SRD5A2 genes are risk factors for PCOS and the severity of hirsutism in affected women.
PCOS and control subjects were genotyped for seven single-nucleotide polymorphisms in SRD5A1 and eight single-nucleotide polymorphisms in SRD5A2. Haplotypes were determined and tested for association with PCOS diagnosis and component phenotypes.
Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; control subjects were recruited from the general surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles.
A total of 287 White women with PCOS and 187 controls participated.
SRD5A1 and SRD5A2 genotype, quantitative hirsutism score, and hormonal and metabolic phenotypes were assessed.
Haplotypes within both genes were associated with PCOS risk. The Leu allele of the Val89Leu variant in SRD5A2 was associated with protection against PCOS; this allele is known to modestly reduce 5alpha-reductase activity. Haplotypes in SRD5A1 but not SRD5A2 were also associated with the degree of hirsutism in affected women.
This study presents genetic evidence suggesting an important role of both isoforms of 5alpha-reductase in the pathogenesis of PCOS. That only SRD5A1 haplotypes were associated with hirsutism suggests that only this isoform is important in the hair follicle. |
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The objective of the study was to test the hypothesis that haplotypes in the SRD5A1 and SRD5A2 genes are risk factors for PCOS and the severity of hirsutism in affected women.
PCOS and control subjects were genotyped for seven single-nucleotide polymorphisms in SRD5A1 and eight single-nucleotide polymorphisms in SRD5A2. Haplotypes were determined and tested for association with PCOS diagnosis and component phenotypes.
Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; control subjects were recruited from the general surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles.
A total of 287 White women with PCOS and 187 controls participated.
SRD5A1 and SRD5A2 genotype, quantitative hirsutism score, and hormonal and metabolic phenotypes were assessed.
Haplotypes within both genes were associated with PCOS risk. The Leu allele of the Val89Leu variant in SRD5A2 was associated with protection against PCOS; this allele is known to modestly reduce 5alpha-reductase activity. Haplotypes in SRD5A1 but not SRD5A2 were also associated with the degree of hirsutism in affected women.
This study presents genetic evidence suggesting an important role of both isoforms of 5alpha-reductase in the pathogenesis of PCOS. That only SRD5A1 haplotypes were associated with hirsutism suggests that only this isoform is important in the hair follicle.</description><identifier>ISSN: 0021-972X</identifier><identifier>PMID: 16849416</identifier><language>eng</language><publisher>United States</publisher><subject>3-Oxo-5-alpha-Steroid 4-Dehydrogenase - genetics ; Adolescent ; Adult ; Female ; Haplotypes ; Hirsutism - genetics ; Humans ; Isoenzymes - genetics ; Middle Aged ; Polycystic Ovary Syndrome - genetics ; Polymorphism, Single Nucleotide ; Risk Factors</subject><ispartof>The journal of clinical endocrinology and metabolism, 2006-10, Vol.91 (10), p.4085-4091</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16849416$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Goodarzi, Mark O</creatorcontrib><creatorcontrib>Shah, Nissar A</creatorcontrib><creatorcontrib>Antoine, Heath J</creatorcontrib><creatorcontrib>Pall, Marita</creatorcontrib><creatorcontrib>Guo, Xiuqing</creatorcontrib><creatorcontrib>Azziz, Ricardo</creatorcontrib><title>Variants in the 5alpha-reductase type 1 and type 2 genes are associated with polycystic ovary syndrome and the severity of hirsutism in affected women</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Despite the importance of dihydrotestosterone in androgen action, polymorphisms in the genes for the two isoforms of 5alpha-reductase (SRD5A1 and SRD5A2) have not been evaluated as risk factors for polycystic ovary syndrome (PCOS).
The objective of the study was to test the hypothesis that haplotypes in the SRD5A1 and SRD5A2 genes are risk factors for PCOS and the severity of hirsutism in affected women.
PCOS and control subjects were genotyped for seven single-nucleotide polymorphisms in SRD5A1 and eight single-nucleotide polymorphisms in SRD5A2. Haplotypes were determined and tested for association with PCOS diagnosis and component phenotypes.
Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; control subjects were recruited from the general surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles.
A total of 287 White women with PCOS and 187 controls participated.
SRD5A1 and SRD5A2 genotype, quantitative hirsutism score, and hormonal and metabolic phenotypes were assessed.
Haplotypes within both genes were associated with PCOS risk. The Leu allele of the Val89Leu variant in SRD5A2 was associated with protection against PCOS; this allele is known to modestly reduce 5alpha-reductase activity. Haplotypes in SRD5A1 but not SRD5A2 were also associated with the degree of hirsutism in affected women.
This study presents genetic evidence suggesting an important role of both isoforms of 5alpha-reductase in the pathogenesis of PCOS. That only SRD5A1 haplotypes were associated with hirsutism suggests that only this isoform is important in the hair follicle.</description><subject>3-Oxo-5-alpha-Steroid 4-Dehydrogenase - genetics</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Female</subject><subject>Haplotypes</subject><subject>Hirsutism - genetics</subject><subject>Humans</subject><subject>Isoenzymes - genetics</subject><subject>Middle Aged</subject><subject>Polycystic Ovary Syndrome - genetics</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Risk Factors</subject><issn>0021-972X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kMtOwzAQRbMA0VL4BeQVu0iJH6m9RBUvqRKbCrGLpvaEGOWFxynKj_C9BFpWM4sz5-rOWbLMMp6nZs3fFskl0UeW5VIqcZEs8kJLI_NimXy_QvDQRWK-Y7FGpqAZakgDutFGIGRxGpDlDDp3XDl7xw6JQUAGRL31ENGxLx9rNvTNZCeK3rL-AGFiNHUu9C0ez2c94QGDjxPrK1b7QGP01P5mQ1Wh_RPNeHeVnFfQEF6f5irZPdzvNk_p9uXxeXO3TQcli7RQYDXnJhNOSQtgueAgtRVKin2lBTpnjHROWG21MHZdrY0z1V5xlZkcQKyS26N2CP3niBTL1pPFpoEO-5HKQhuhRZHN4M0JHPctunIIvp37lf-PFD_ifnFE</recordid><startdate>200610</startdate><enddate>200610</enddate><creator>Goodarzi, Mark O</creator><creator>Shah, Nissar A</creator><creator>Antoine, Heath J</creator><creator>Pall, Marita</creator><creator>Guo, Xiuqing</creator><creator>Azziz, Ricardo</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>200610</creationdate><title>Variants in the 5alpha-reductase type 1 and type 2 genes are associated with polycystic ovary syndrome and the severity of hirsutism in affected women</title><author>Goodarzi, Mark O ; Shah, Nissar A ; Antoine, Heath J ; Pall, Marita ; Guo, Xiuqing ; Azziz, Ricardo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p546-65ac822903d54caac232a48c3543bf83edd994dd3c8c839c7f79d9fb525091aa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>3-Oxo-5-alpha-Steroid 4-Dehydrogenase - genetics</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Female</topic><topic>Haplotypes</topic><topic>Hirsutism - genetics</topic><topic>Humans</topic><topic>Isoenzymes - genetics</topic><topic>Middle Aged</topic><topic>Polycystic Ovary Syndrome - genetics</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Risk Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Goodarzi, Mark O</creatorcontrib><creatorcontrib>Shah, Nissar A</creatorcontrib><creatorcontrib>Antoine, Heath J</creatorcontrib><creatorcontrib>Pall, Marita</creatorcontrib><creatorcontrib>Guo, Xiuqing</creatorcontrib><creatorcontrib>Azziz, Ricardo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Goodarzi, Mark O</au><au>Shah, Nissar A</au><au>Antoine, Heath J</au><au>Pall, Marita</au><au>Guo, Xiuqing</au><au>Azziz, Ricardo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Variants in the 5alpha-reductase type 1 and type 2 genes are associated with polycystic ovary syndrome and the severity of hirsutism in affected women</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2006-10</date><risdate>2006</risdate><volume>91</volume><issue>10</issue><spage>4085</spage><epage>4091</epage><pages>4085-4091</pages><issn>0021-972X</issn><abstract>Despite the importance of dihydrotestosterone in androgen action, polymorphisms in the genes for the two isoforms of 5alpha-reductase (SRD5A1 and SRD5A2) have not been evaluated as risk factors for polycystic ovary syndrome (PCOS).
The objective of the study was to test the hypothesis that haplotypes in the SRD5A1 and SRD5A2 genes are risk factors for PCOS and the severity of hirsutism in affected women.
PCOS and control subjects were genotyped for seven single-nucleotide polymorphisms in SRD5A1 and eight single-nucleotide polymorphisms in SRD5A2. Haplotypes were determined and tested for association with PCOS diagnosis and component phenotypes.
Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; control subjects were recruited from the general surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles.
A total of 287 White women with PCOS and 187 controls participated.
SRD5A1 and SRD5A2 genotype, quantitative hirsutism score, and hormonal and metabolic phenotypes were assessed.
Haplotypes within both genes were associated with PCOS risk. The Leu allele of the Val89Leu variant in SRD5A2 was associated with protection against PCOS; this allele is known to modestly reduce 5alpha-reductase activity. Haplotypes in SRD5A1 but not SRD5A2 were also associated with the degree of hirsutism in affected women.
This study presents genetic evidence suggesting an important role of both isoforms of 5alpha-reductase in the pathogenesis of PCOS. That only SRD5A1 haplotypes were associated with hirsutism suggests that only this isoform is important in the hair follicle.</abstract><cop>United States</cop><pmid>16849416</pmid><tpages>7</tpages></addata></record> |
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source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals |
subjects | 3-Oxo-5-alpha-Steroid 4-Dehydrogenase - genetics Adolescent Adult Female Haplotypes Hirsutism - genetics Humans Isoenzymes - genetics Middle Aged Polycystic Ovary Syndrome - genetics Polymorphism, Single Nucleotide Risk Factors |
title | Variants in the 5alpha-reductase type 1 and type 2 genes are associated with polycystic ovary syndrome and the severity of hirsutism in affected women |
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