Variants in SULT2A1 Affect the DHEA Sulphate to DHEA Ratio in Patients With Polycystic Ovary Syndrome But Not the Hyperandrogenic Phenotype
Context: Because of the elevated dehydroepiandrosterone sulfate (DHEAS) levels in polycystic ovary syndrome (PCOS) and the heritability of DHEAS serum levels, genes encoding the enzymes that control the sulfation of dehydroepiandrosterone (DHEA) to DHEAS and vice versa are obvious candidate genes to...
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| Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2013-09, Vol.98 (9), p.3848-3855 |
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| container_title | The journal of clinical endocrinology and metabolism |
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| creator | Louwers, Yvonne V de Jong, Frank H van Herwaarden, Nathalie A. A Stolk, Lisette Fauser, Bart C. J. M Uitterlinden, André G Laven, Joop S. E |
| description | Context:
Because of the elevated dehydroepiandrosterone sulfate (DHEAS) levels in polycystic ovary syndrome (PCOS) and the heritability of DHEAS serum levels, genes encoding the enzymes that control the sulfation of dehydroepiandrosterone (DHEA) to DHEAS and vice versa are obvious candidate genes to explain part of the heritability of PCOS.
Objective:
The objective of the study was to determine the role of genetic variants in sulfotransferase (SULT2A1), 3-phosphoadenosine 5-phosphosulfate synthase isoform 2 (PAPSS2), and steroid sulfatase (STS) in PCOS and in hormone levels related to the hyperandrogenic phenotype of PCOS.
Design:
This was a candidate-gene study.
Patients:
The discovery set consisted of 582 patients and 2017 controls.
Main Outcome Measures:
A pruned subset of 28 single-nucleotide polymorphisms (SNPs) in SULT2A1, PAPSS2, and STS was generated based on pairwise genotypic correlation. Association with PCOS was tested, and we studied whether the SNPs modulate DHEAS levels, DHEA levels, and their ratio in PCOS. Significant SNPs were replicated in an independent sample of patients.
Results:
None of the SNPs in SULT2A1, PAPSS2, and STS constituted risk alleles for PCOS. SNP rs2910397 in SULT2A1 decreased the DHEAS to DHEA ratio in PCOS by 5% in the discovery sample. Meta-analysis of discovery and replication sample resulted in a combined effect of −0.095 (P = .027). However, carrying the minor T allele did not contribute to differences in the hyperandrogenic phenotype, including the levels of T and androstenedione, of PCOS patients.
Conclusions:
Genetic variants in SULT2A1, PAPSS2, and STS do not predispose to PCOS. Although a variant in SULT2A1 decreased the DHEAS to DHEA ratio, no changes in other androgenic hormone levels were observed. |
| doi_str_mv | 10.1210/jc.2013-1976 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1431299080</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1431299080</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4481-8d9406447087a014992d4a82db31981f7ac88234dcfe8493fe703a1e77a81f263</originalsourceid><addsrcrecordid>eNptkE1v1DAQhi0Eokvhxhn5gsSBFH81to_bUlikFV2xLXCzXGdCsmTjYDtU-xv40zjKAhd8sWfmeWc8L0LPKTmjjJI3O3fGCOUF1bJ8gBZUi_NC5uAhWhDCaKEl-3qCnsS4I4QKcc4foxPGVUlFyRbo12cbWtuniNseb2_XN2xJ8bKuwSWcGsBvV1dLvB27obEJcPJz4pNNrZ8Um_yASf2lTQ3e-O7gDjG1Dl__tOGAt4e-Cn4P-GJM-KOfW64OAwQ7Fb5Bn9FNA71POfkUPaptF-HZ8T5Ft--ubi5Xxfr6_YfL5bpwQihaqEoLUgohiZI2r6Q1q4RVrLrjVCtaS-uUYlxUrgYlNK9BEm4pSGlzlZX8FL2a-w7B_xghJrNvo4Ousz34MRoqOGVaE0Uy-npGXfAxBqjNENp9Xs1QYib7zc6ZyX4z2Z_xF8fO490eqr_wH78z8PII2OhsV2cfXBv_cVIyJonOnJi5e98lCPF7N95DMA3YLjWG5CNKqYppMtE5KqYMzTI-y6CvvAttD0OAGM3Oj6HPlv7_178BFTesKQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1431299080</pqid></control><display><type>article</type><title>Variants in SULT2A1 Affect the DHEA Sulphate to DHEA Ratio in Patients With Polycystic Ovary Syndrome But Not the Hyperandrogenic Phenotype</title><source>MEDLINE</source><source>Journals@Ovid Complete</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Louwers, Yvonne V ; de Jong, Frank H ; van Herwaarden, Nathalie A. A ; Stolk, Lisette ; Fauser, Bart C. J. M ; Uitterlinden, André G ; Laven, Joop S. E</creator><creatorcontrib>Louwers, Yvonne V ; de Jong, Frank H ; van Herwaarden, Nathalie A. A ; Stolk, Lisette ; Fauser, Bart C. J. M ; Uitterlinden, André G ; Laven, Joop S. E</creatorcontrib><description>Context:
Because of the elevated dehydroepiandrosterone sulfate (DHEAS) levels in polycystic ovary syndrome (PCOS) and the heritability of DHEAS serum levels, genes encoding the enzymes that control the sulfation of dehydroepiandrosterone (DHEA) to DHEAS and vice versa are obvious candidate genes to explain part of the heritability of PCOS.
Objective:
The objective of the study was to determine the role of genetic variants in sulfotransferase (SULT2A1), 3-phosphoadenosine 5-phosphosulfate synthase isoform 2 (PAPSS2), and steroid sulfatase (STS) in PCOS and in hormone levels related to the hyperandrogenic phenotype of PCOS.
Design:
This was a candidate-gene study.
Patients:
The discovery set consisted of 582 patients and 2017 controls.
Main Outcome Measures:
A pruned subset of 28 single-nucleotide polymorphisms (SNPs) in SULT2A1, PAPSS2, and STS was generated based on pairwise genotypic correlation. Association with PCOS was tested, and we studied whether the SNPs modulate DHEAS levels, DHEA levels, and their ratio in PCOS. Significant SNPs were replicated in an independent sample of patients.
Results:
None of the SNPs in SULT2A1, PAPSS2, and STS constituted risk alleles for PCOS. SNP rs2910397 in SULT2A1 decreased the DHEAS to DHEA ratio in PCOS by 5% in the discovery sample. Meta-analysis of discovery and replication sample resulted in a combined effect of −0.095 (P = .027). However, carrying the minor T allele did not contribute to differences in the hyperandrogenic phenotype, including the levels of T and androstenedione, of PCOS patients.
Conclusions:
Genetic variants in SULT2A1, PAPSS2, and STS do not predispose to PCOS. Although a variant in SULT2A1 decreased the DHEAS to DHEA ratio, no changes in other androgenic hormone levels were observed.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/jc.2013-1976</identifier><identifier>PMID: 23861462</identifier><identifier>CODEN: JCEMAZ</identifier><language>eng</language><publisher>Bethesda, MD: Endocrine Society</publisher><subject>Adult ; Alleles ; Biological and medical sciences ; Dehydroepiandrosterone - blood ; Dehydroepiandrosterone Sulfate - blood ; Endocrinopathies ; Feeding. Feeding behavior ; Female ; Fundamental and applied biological sciences. Psychology ; Genetic Predisposition to Disease ; Genotype ; Humans ; Hyperandrogenism - blood ; Hyperandrogenism - genetics ; Medical sciences ; Multienzyme Complexes - genetics ; Polycystic Ovary Syndrome - blood ; Polycystic Ovary Syndrome - genetics ; Polymorphism, Single Nucleotide ; Steryl-Sulfatase - genetics ; Sulfate Adenylyltransferase - genetics ; Sulfotransferases - genetics ; Vertebrates: anatomy and physiology, studies on body, several organs or systems ; Vertebrates: endocrinology</subject><ispartof>The journal of clinical endocrinology and metabolism, 2013-09, Vol.98 (9), p.3848-3855</ispartof><rights>Copyright © 2013 by The Endocrine Society</rights><rights>2014 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4481-8d9406447087a014992d4a82db31981f7ac88234dcfe8493fe703a1e77a81f263</citedby><cites>FETCH-LOGICAL-c4481-8d9406447087a014992d4a82db31981f7ac88234dcfe8493fe703a1e77a81f263</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27722709$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23861462$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Louwers, Yvonne V</creatorcontrib><creatorcontrib>de Jong, Frank H</creatorcontrib><creatorcontrib>van Herwaarden, Nathalie A. A</creatorcontrib><creatorcontrib>Stolk, Lisette</creatorcontrib><creatorcontrib>Fauser, Bart C. J. M</creatorcontrib><creatorcontrib>Uitterlinden, André G</creatorcontrib><creatorcontrib>Laven, Joop S. E</creatorcontrib><title>Variants in SULT2A1 Affect the DHEA Sulphate to DHEA Ratio in Patients With Polycystic Ovary Syndrome But Not the Hyperandrogenic Phenotype</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Context:
Because of the elevated dehydroepiandrosterone sulfate (DHEAS) levels in polycystic ovary syndrome (PCOS) and the heritability of DHEAS serum levels, genes encoding the enzymes that control the sulfation of dehydroepiandrosterone (DHEA) to DHEAS and vice versa are obvious candidate genes to explain part of the heritability of PCOS.
Objective:
The objective of the study was to determine the role of genetic variants in sulfotransferase (SULT2A1), 3-phosphoadenosine 5-phosphosulfate synthase isoform 2 (PAPSS2), and steroid sulfatase (STS) in PCOS and in hormone levels related to the hyperandrogenic phenotype of PCOS.
Design:
This was a candidate-gene study.
Patients:
The discovery set consisted of 582 patients and 2017 controls.
Main Outcome Measures:
A pruned subset of 28 single-nucleotide polymorphisms (SNPs) in SULT2A1, PAPSS2, and STS was generated based on pairwise genotypic correlation. Association with PCOS was tested, and we studied whether the SNPs modulate DHEAS levels, DHEA levels, and their ratio in PCOS. Significant SNPs were replicated in an independent sample of patients.
Results:
None of the SNPs in SULT2A1, PAPSS2, and STS constituted risk alleles for PCOS. SNP rs2910397 in SULT2A1 decreased the DHEAS to DHEA ratio in PCOS by 5% in the discovery sample. Meta-analysis of discovery and replication sample resulted in a combined effect of −0.095 (P = .027). However, carrying the minor T allele did not contribute to differences in the hyperandrogenic phenotype, including the levels of T and androstenedione, of PCOS patients.
Conclusions:
Genetic variants in SULT2A1, PAPSS2, and STS do not predispose to PCOS. Although a variant in SULT2A1 decreased the DHEAS to DHEA ratio, no changes in other androgenic hormone levels were observed.</description><subject>Adult</subject><subject>Alleles</subject><subject>Biological and medical sciences</subject><subject>Dehydroepiandrosterone - blood</subject><subject>Dehydroepiandrosterone Sulfate - blood</subject><subject>Endocrinopathies</subject><subject>Feeding. Feeding behavior</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotype</subject><subject>Humans</subject><subject>Hyperandrogenism - blood</subject><subject>Hyperandrogenism - genetics</subject><subject>Medical sciences</subject><subject>Multienzyme Complexes - genetics</subject><subject>Polycystic Ovary Syndrome - blood</subject><subject>Polycystic Ovary Syndrome - genetics</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Steryl-Sulfatase - genetics</subject><subject>Sulfate Adenylyltransferase - genetics</subject><subject>Sulfotransferases - genetics</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><subject>Vertebrates: endocrinology</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkE1v1DAQhi0Eokvhxhn5gsSBFH81to_bUlikFV2xLXCzXGdCsmTjYDtU-xv40zjKAhd8sWfmeWc8L0LPKTmjjJI3O3fGCOUF1bJ8gBZUi_NC5uAhWhDCaKEl-3qCnsS4I4QKcc4foxPGVUlFyRbo12cbWtuniNseb2_XN2xJ8bKuwSWcGsBvV1dLvB27obEJcPJz4pNNrZ8Um_yASf2lTQ3e-O7gDjG1Dl__tOGAt4e-Cn4P-GJM-KOfW64OAwQ7Fb5Bn9FNA71POfkUPaptF-HZ8T5Ft--ubi5Xxfr6_YfL5bpwQihaqEoLUgohiZI2r6Q1q4RVrLrjVCtaS-uUYlxUrgYlNK9BEm4pSGlzlZX8FL2a-w7B_xghJrNvo4Ousz34MRoqOGVaE0Uy-npGXfAxBqjNENp9Xs1QYib7zc6ZyX4z2Z_xF8fO490eqr_wH78z8PII2OhsV2cfXBv_cVIyJonOnJi5e98lCPF7N95DMA3YLjWG5CNKqYppMtE5KqYMzTI-y6CvvAttD0OAGM3Oj6HPlv7_178BFTesKQ</recordid><startdate>201309</startdate><enddate>201309</enddate><creator>Louwers, Yvonne V</creator><creator>de Jong, Frank H</creator><creator>van Herwaarden, Nathalie A. A</creator><creator>Stolk, Lisette</creator><creator>Fauser, Bart C. J. M</creator><creator>Uitterlinden, André G</creator><creator>Laven, Joop S. E</creator><general>Endocrine Society</general><general>Copyright by 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>7X8</scope></search><sort><creationdate>201309</creationdate><title>Variants in SULT2A1 Affect the DHEA Sulphate to DHEA Ratio in Patients With Polycystic Ovary Syndrome But Not the Hyperandrogenic Phenotype</title><author>Louwers, Yvonne V ; de Jong, Frank H ; van Herwaarden, Nathalie A. A ; Stolk, Lisette ; Fauser, Bart C. J. M ; Uitterlinden, André G ; Laven, Joop S. E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4481-8d9406447087a014992d4a82db31981f7ac88234dcfe8493fe703a1e77a81f263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Alleles</topic><topic>Biological and medical sciences</topic><topic>Dehydroepiandrosterone - blood</topic><topic>Dehydroepiandrosterone Sulfate - blood</topic><topic>Endocrinopathies</topic><topic>Feeding. Feeding behavior</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genetic Predisposition to Disease</topic><topic>Genotype</topic><topic>Humans</topic><topic>Hyperandrogenism - blood</topic><topic>Hyperandrogenism - genetics</topic><topic>Medical sciences</topic><topic>Multienzyme Complexes - genetics</topic><topic>Polycystic Ovary Syndrome - blood</topic><topic>Polycystic Ovary Syndrome - genetics</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Steryl-Sulfatase - genetics</topic><topic>Sulfate Adenylyltransferase - genetics</topic><topic>Sulfotransferases - genetics</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Louwers, Yvonne V</creatorcontrib><creatorcontrib>de Jong, Frank H</creatorcontrib><creatorcontrib>van Herwaarden, Nathalie A. A</creatorcontrib><creatorcontrib>Stolk, Lisette</creatorcontrib><creatorcontrib>Fauser, Bart C. J. M</creatorcontrib><creatorcontrib>Uitterlinden, André G</creatorcontrib><creatorcontrib>Laven, Joop S. E</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>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>Louwers, Yvonne V</au><au>de Jong, Frank H</au><au>van Herwaarden, Nathalie A. A</au><au>Stolk, Lisette</au><au>Fauser, Bart C. J. M</au><au>Uitterlinden, André G</au><au>Laven, Joop S. E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Variants in SULT2A1 Affect the DHEA Sulphate to DHEA Ratio in Patients With Polycystic Ovary Syndrome But Not the Hyperandrogenic Phenotype</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2013-09</date><risdate>2013</risdate><volume>98</volume><issue>9</issue><spage>3848</spage><epage>3855</epage><pages>3848-3855</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><coden>JCEMAZ</coden><abstract>Context:
Because of the elevated dehydroepiandrosterone sulfate (DHEAS) levels in polycystic ovary syndrome (PCOS) and the heritability of DHEAS serum levels, genes encoding the enzymes that control the sulfation of dehydroepiandrosterone (DHEA) to DHEAS and vice versa are obvious candidate genes to explain part of the heritability of PCOS.
Objective:
The objective of the study was to determine the role of genetic variants in sulfotransferase (SULT2A1), 3-phosphoadenosine 5-phosphosulfate synthase isoform 2 (PAPSS2), and steroid sulfatase (STS) in PCOS and in hormone levels related to the hyperandrogenic phenotype of PCOS.
Design:
This was a candidate-gene study.
Patients:
The discovery set consisted of 582 patients and 2017 controls.
Main Outcome Measures:
A pruned subset of 28 single-nucleotide polymorphisms (SNPs) in SULT2A1, PAPSS2, and STS was generated based on pairwise genotypic correlation. Association with PCOS was tested, and we studied whether the SNPs modulate DHEAS levels, DHEA levels, and their ratio in PCOS. Significant SNPs were replicated in an independent sample of patients.
Results:
None of the SNPs in SULT2A1, PAPSS2, and STS constituted risk alleles for PCOS. SNP rs2910397 in SULT2A1 decreased the DHEAS to DHEA ratio in PCOS by 5% in the discovery sample. Meta-analysis of discovery and replication sample resulted in a combined effect of −0.095 (P = .027). However, carrying the minor T allele did not contribute to differences in the hyperandrogenic phenotype, including the levels of T and androstenedione, of PCOS patients.
Conclusions:
Genetic variants in SULT2A1, PAPSS2, and STS do not predispose to PCOS. Although a variant in SULT2A1 decreased the DHEAS to DHEA ratio, no changes in other androgenic hormone levels were observed.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>23861462</pmid><doi>10.1210/jc.2013-1976</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0021-972X |
| ispartof | The journal of clinical endocrinology and metabolism, 2013-09, Vol.98 (9), p.3848-3855 |
| issn | 0021-972X 1945-7197 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1431299080 |
| source | MEDLINE; Journals@Ovid Complete; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult Alleles Biological and medical sciences Dehydroepiandrosterone - blood Dehydroepiandrosterone Sulfate - blood Endocrinopathies Feeding. Feeding behavior Female Fundamental and applied biological sciences. Psychology Genetic Predisposition to Disease Genotype Humans Hyperandrogenism - blood Hyperandrogenism - genetics Medical sciences Multienzyme Complexes - genetics Polycystic Ovary Syndrome - blood Polycystic Ovary Syndrome - genetics Polymorphism, Single Nucleotide Steryl-Sulfatase - genetics Sulfate Adenylyltransferase - genetics Sulfotransferases - genetics Vertebrates: anatomy and physiology, studies on body, several organs or systems Vertebrates: endocrinology |
| title | Variants in SULT2A1 Affect the DHEA Sulphate to DHEA Ratio in Patients With Polycystic Ovary Syndrome But Not the Hyperandrogenic Phenotype |
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