{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T05:57:53Z","timestamp":1768802273659,"version":"3.49.0"},"reference-count":42,"publisher":"The Endocrine Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,9,1]]},"abstract":"<jats:sec>\n                  <jats:title>Context:<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective:<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design:<\/jats:title>\n                  <jats:p>This was a candidate-gene study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients:<\/jats:title>\n                  <jats:p>The discovery set consisted of 582 patients and 2017 controls.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measures:<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>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 \u22120.095 (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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions:<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jc.2013-1976","type":"journal-article","created":{"date-parts":[[2013,7,17]],"date-time":"2013-07-17T02:17:49Z","timestamp":1374027469000},"page":"3848-3855","source":"Crossref","is-referenced-by-count":25,"title":["Variants in SULT2A1 Affect the DHEA Sulphate to DHEA Ratio in Patients With Polycystic Ovary Syndrome But Not the Hyperandrogenic Phenotype"],"prefix":"10.1210","volume":"98","author":[{"given":"Yvonne V.","family":"Louwers","sequence":"first","affiliation":[{"name":"Division of Reproductive Medicine, Department of Obstetrics and Gynecology (Y.V.L., N.A.A.v.H., J.S.E.L.), 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank H.","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (F.H.d.J., L.S., A.G.U.), 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie A. A.","family":"van Herwaarden","sequence":"additional","affiliation":[{"name":"Division of Reproductive Medicine, Department of Obstetrics and Gynecology (Y.V.L., N.A.A.v.H., J.S.E.L.), 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisette","family":"Stolk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (F.H.d.J., L.S., A.G.U.), 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart C. J. M.","family":"Fauser","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine and Gynecology (B.C.J.M.F.), University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9 G.","family":"Uitterlinden","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (F.H.d.J., L.S., A.G.U.), 3000 CA Rotterdam, The Netherlands"},{"name":"Department of Epidemiology (A.G.U.), Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joop S. E.","family":"Laven","sequence":"additional","affiliation":[{"name":"Division of Reproductive Medicine, Department of Obstetrics and Gynecology (Y.V.L., N.A.A.v.H., J.S.E.L.), 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071615455929700_B1","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1016\/j.fertnstert.2008.12.138","article-title":"Prevalence of hyperandrogenemia in the polycystic ovary syndrome diagnosed by the National Institutes of Health 1990 criteria","volume":"93","author":"Huang","year":"2010","journal-title":"Fertil Steril"},{"key":"2020071615455929700_B2","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1210\/jc.2010-0130","article-title":"Hyperandrogenism in women with polycystic ovary syndrome persists after menopause","volume":"96","author":"Markopoulos","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615455929700_B3","doi-asserted-by":"crossref","first-page":"2134","DOI":"10.1210\/jcem.87.5.8387","article-title":"Elevated dehydroepiandrosterone sulfate levels as the reproductive phenotype in the brothers of women with polycystic ovary syndrome","volume":"87","author":"Legro","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615455929700_B4","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1016\/j.fertnstert.2006.05.045","article-title":"Heritability of dehydroepiandrosterone sulfate in women with polycystic ovary syndrome and their sisters","volume":"86","author":"Yildiz","year":"2006","journal-title":"Fertil Steril"},{"key":"2020071615455929700_B5","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/BF03347408","article-title":"Prevalence and metabolic characteristics of adrenal androgen excess in hyperandrogenic women with different phenotypes","volume":"30","author":"Carmina","year":"2007","journal-title":"J Endocrinol Invest"},{"key":"2020071615455929700_B6","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1210\/jc.2008-2583","article-title":"Adrenal androgen production capacity remains high up to menopause in women with polycystic ovary syndrome","volume":"94","author":"Puurunen","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615455929700_B7","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1210\/jcem.87.2.8240","article-title":"Genetics of serum dehydroepiandrosterone sulfate and its relationship to insulin in a population-based cohort of twin subjects","volume":"87","author":"Nestler","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615455929700_B8","first-page":"69","article-title":"Dehydroepiandrosterone sulfate as an indicator of adrenal androgen function","volume":"57","author":"Lobo","year":"1981","journal-title":"Obstet Gynecol"},{"key":"2020071615455929700_B9","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1210\/jcem-39-2-340","article-title":"Ovarian and adrenal contribution to peripheral androgens during the menstrual cycle","volume":"39","author":"Abraham","year":"1974","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615455929700_B10","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1210\/jcem-17-9-1051","article-title":"Dehydroepiandrosterone and androsterone levels in human plasma: effect of age and sex; day-to-day and diurnal variations","volume":"17","author":"Migeon","year":"1957","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615455929700_B11","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1111\/j.1365-2265.2005.02256.x","article-title":"Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (PCOS)","volume":"62","author":"Kumar","year":"2005","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071615455929700_B12","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0029-7844(95)00065-Y","article-title":"Reassessment of adrenal androgen secretion in women with polycystic ovary syndrome","volume":"85","author":"Carmina","year":"1995","journal-title":"Obstet Gynecol"},{"key":"2020071615455929700_B13","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1055\/s-2007-1016296","article-title":"Adrenal involvement in polycystic ovary syndrome","volume":"15","author":"Gonzalez","year":"1997","journal-title":"Semin Reprod Endocrinol"},{"key":"2020071615455929700_B14","doi-asserted-by":"crossref","first-page":"C113","DOI":"10.1016\/0303-7207(91)90116-A","article-title":"Intracrinology","volume":"78","author":"Labrie","year":"1991","journal-title":"Mol Cell Endocrinol"},{"key":"2020071615455929700_B15","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1210\/er.2010-0013","article-title":"The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders","volume":"32","author":"Miller","year":"2011","journal-title":"Endocr Rev"},{"key":"2020071615455929700_B16","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1210\/er.2001-0040","article-title":"Sulfonation and molecular action","volume":"23","author":"Strott","year":"2002","journal-title":"Endocr Rev"},{"key":"2020071615455929700_B17","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1210\/jc.2006-2600","article-title":"Genes for enzymes regulating dehydroepiandrosterone sulfonation are associated with levels of dehydroepiandrosterone sulfate in polycystic ovary syndrome","volume":"92","author":"Goodarzi","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615455929700_B18","first-page":"671","article-title":"Premature adrenarche\u2014normal variant or forerunner of adult disease?","volume":"21","author":"Ibanez","year":"2000","journal-title":"Endocr Rev"},{"key":"2020071615455929700_B19","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1056\/NEJMoa0810489","article-title":"Inactivating PAPSS2 mutations in a patient with premature pubarche","volume":"360","author":"Noordam","year":"2009","journal-title":"N Engl J Med"},{"key":"2020071615455929700_B20","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.fertnstert.2003.10.004","article-title":"Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome","volume":"81","year":"2004","journal-title":"Fertil Steril"},{"key":"2020071615455929700_B21","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/humrep\/deh098","article-title":"Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS)","volume":"19","year":"2004","journal-title":"Hum Reprod"},{"key":"2020071615455929700_B22","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/s10654-007-9199-x","article-title":"The Rotterdam Study: objectives and design update","volume":"22","author":"Hofman","year":"2007","journal-title":"Eur J Epidemiol"},{"key":"2020071615455929700_B23","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: a tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"key":"2020071615455929700_B24","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1002\/gepi.20533","article-title":"MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes","volume":"34","author":"Li","year":"2010","journal-title":"Genet Epidemiol"},{"key":"2020071615455929700_B25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1469-1809.2010.00618.x","article-title":"Modeling interactions with known risk loci\u2014a Bayesian model averaging approach","volume":"75","author":"Ferreira","year":"2011","journal-title":"Ann Hum Genet"},{"key":"2020071615455929700_B26","unstructured":"R Development Core Team. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2012. http:\/\/www.R-project.org"},{"key":"2020071615455929700_B27","doi-asserted-by":"crossref","first-page":"3600","DOI":"10.1210\/jc.2004-2386","article-title":"No evidence for hepatic conversion of dehydroepiandrosterone (DHEA) sulfate to DHEA: in vivo and in vitro studies","volume":"90","author":"Hammer","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615455929700_B28","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1210\/jc.2005-2258","article-title":"Dissociation of serum dehydroepiandrosterone and dehydroepiandrosterone sulfate in septic shock","volume":"91","author":"Arlt","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615455929700_B29","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/ng.732","article-title":"Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3","volume":"43","author":"Chen","year":"2011","journal-title":"Nat Genet"},{"key":"2020071615455929700_B30","doi-asserted-by":"crossref","first-page":"E1342","DOI":"10.1210\/jc.2011-3478","article-title":"Variants in DENND1A are associated with polycystic ovary syndrome in women of European ancestry","volume":"97","author":"Welt","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615455929700_B31","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.jsbmb.2012.02.003","article-title":"The expression of sex steroid synthesis and inactivation enzymes in subcutaneous adipose tissue of PCOS patients","volume":"132","author":"Wang","year":"2012","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2020071615455929700_B32","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.steroids.2006.05.005","article-title":"Steroidogenic alterations and adrenal androgen excess in PCOS","volume":"71","author":"Doi","year":"2006","journal-title":"Steroids"},{"key":"2020071615455929700_B33","doi-asserted-by":"crossref","first-page":"2760","DOI":"10.1210\/jc.2002-021875","article-title":"Beyond adrenal and ovarian androgen generation: increased peripheral 5\u03b1-reductase activity in women with polycystic ovary syndrome","volume":"88","author":"Fassnacht","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615455929700_B34","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1056\/NEJM199402173300703","article-title":"Hyperandrogenism in polycystic ovary syndrome. Evidence of dysregulation of 11\u03b2-hydroxysteroid dehydrogenase","volume":"330","author":"Rodin","year":"1994","journal-title":"N Engl J Med"},{"key":"2020071615455929700_B35","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/0140-6736(90)90664-Q","article-title":"5\u03b1-Reductase activity in polycystic ovary syndrome","volume":"335","author":"Stewart","year":"1990","journal-title":"Lancet"},{"key":"2020071615455929700_B36","doi-asserted-by":"crossref","first-page":"5907","DOI":"10.1210\/jc.2003-030240","article-title":"Altered cortisol metabolism in polycystic ovary syndrome: insulin enhances 5\u03b1-reduction but not the elevated adrenal steroid production rates","volume":"88","author":"Tsilchorozidou","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615455929700_B37","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1210\/jc.2005-2222","article-title":"Genetic variation in 11\u03b2-hydroxysteroid dehydrogenase type 1 predicts adrenal hyperandrogenism among lean women with polycystic ovary syndrome","volume":"91","author":"Gambineri","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615455929700_B38","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.1210\/jc.2008-0403","article-title":"Association of CYP3A7*1C and serum dehydroepiandrosterone sulfate levels in women with polycystic ovary syndrome","volume":"93","author":"Goodarzi","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615455929700_B39","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1124\/dmd.32.3.305","article-title":"Stereo- and regioselectivity account for the diversity of dehydroepiandrosterone (DHEA) metabolites produced by liver microsomal cytochromes P450","volume":"32","author":"Miller","year":"2004","journal-title":"Drug Metab Dispos"},{"key":"2020071615455929700_B40","doi-asserted-by":"crossref","first-page":"5313","DOI":"10.1210\/jc.2005-0307","article-title":"A common polymorphism in the CYP3A7 gene is associated with a nearly 50% reduction in serum dehydroepiandrosterone sulfate levels","volume":"90","author":"Smit","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615455929700_B41","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/86882","article-title":"Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression","volume":"27","author":"Kuehl","year":"2001","journal-title":"Nat Genet"},{"key":"2020071615455929700_B42","doi-asserted-by":"crossref","first-page":"e1002025","DOI":"10.1371\/journal.pgen.1002025","article-title":"Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms","volume":"7","author":"Zhai","year":"2011","journal-title":"PLoS Genet"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/98\/9\/3848\/11127689\/jcem3848.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/98\/9\/3848\/11127689\/jcem3848.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T02:55:00Z","timestamp":1594954500000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/98\/9\/3848\/2833607"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,9,1]]},"references-count":42,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2013,9,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2013-1976","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,9,1]]}}}