{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T06:03:05Z","timestamp":1785045785913,"version":"3.55.0"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,6,6]],"date-time":"2012-06-06T00:00:00Z","timestamp":1338940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2012,7]]},"abstract":"Summary<\/jats:title>Objective<\/jats:title>Polycystic ovary syndrome (PCOS<\/jats:styled-content>) is a frequent condition, affecting about 15% of women of reproductive age. Because of its familial occurrence, a multifactorial model of susceptibility, including both genetic and environmental factors, has been proposed. However, the identification of genetic factors has been elusive.<\/jats:p><\/jats:sec>Design<\/jats:title>Case\u2013control study aimed at evaluating possible associations between functionally relevant variants of the luteinizing hormone\/choriogonadotrophin receptor gene (LHCGR<\/jats:italic><\/jats:styled-content>) and PCOS<\/jats:styled-content> phenotype.<\/jats:p><\/jats:sec>Patients<\/jats:title>A total of 198 PCOS<\/jats:styled-content> and 187 non\u2010PCOS<\/jats:styled-content> women, aged 14\u201335\u00a0years, of Sardinian origin, were referred to the outpatient clinic of the D<\/jats:styled-content>epartment of O<\/jats:styled-content>bstetrics and G<\/jats:styled-content>ynaecology of the U<\/jats:styled-content>niversity of C<\/jats:styled-content>agliari (S<\/jats:styled-content>ardinia). PCOS<\/jats:styled-content> diagnosis was based on the R<\/jats:styled-content>otterdam criteria.<\/jats:p><\/jats:sec>Measurements<\/jats:title>We determined the genotype of ins18LQ<\/jats:styled-content>, S<\/jats:styled-content>291N<\/jats:styled-content> and S312N<\/jats:styled-content> variants at the LHCGR<\/jats:italic><\/jats:styled-content> locus. Genotype was related to the presence or absence of PCOS<\/jats:styled-content> and to several clinical and biochemical characteristics.<\/jats:p><\/jats:sec>Results<\/jats:title>The presence of at least one 312N<\/jats:styled-content> allele was strongly associated with PCOS<\/jats:styled-content> risk (OR<\/jats:styled-content>, 2\u00b704; 95% CI<\/jats:styled-content>, 1\u00b732\u20133\u00b714; \u03c72<\/jats:sup>, 10\u00b747; P<\/jats:italic>\u00a0=\u00a00\u00b7001). 312N<\/jats:styled-content> homozygosity was associated with a further risk increase (OR<\/jats:styled-content>, 2\u00b773; 95% CI<\/jats:styled-content>, 1\u00b725\u20135\u00b795; \u03c72<\/jats:sup>, 6\u00b765; P<\/jats:italic>\u00a0=\u00a00\u00b701). The number of ins18LQ<\/jats:styled-content> alleles was associated with LH<\/jats:styled-content> serum levels in controls (\u03c72<\/jats:sup>, 8\u00b704, P<\/jats:italic>\u00a0=\u00a00\u00b7017).<\/jats:p><\/jats:sec>Conclusions<\/jats:title>For the first time, we have identified a genetic variant that is strongly associated with PCOS<\/jats:styled-content> in an isolated population. These results, if confirmed in other cohorts, may provide the opportunity to test the S312N<\/jats:styled-content> genotype at the LHCGR<\/jats:italic><\/jats:styled-content> locus in fertile women to assess the risk of PCOS<\/jats:styled-content>. The avoidance of triggering factors like weight increase may improve the reproductive outcome of potentially at\u2010risk subjects.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2265.2012.04372.x","type":"journal-article","created":{"date-parts":[[2012,2,22]],"date-time":"2012-02-22T19:48:34Z","timestamp":1329940114000},"page":"113-119","source":"Crossref","is-referenced-by-count":50,"title":["The 312N<\/scp> variant of the luteinizing hormone\/choriogonadotropin receptor gene (LHCGR<\/i><\/scp>) confers up to 2\u00b77\u2010fold increased risk of polycystic ovary syndrome in a S<\/scp>ardinian population"],"prefix":"10.1111","volume":"77","author":[{"given":"A.","family":"Capalbo","sequence":"first","affiliation":[{"name":"Istituto di Genetica Medica Universit\u00e0 Cattolica del Sacro Cuore Roma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Sagnella","sequence":"additional","affiliation":[{"name":"Dipartimento di Ostetricia e Ginecologia Universit\u00e0 Cattolica del Sacro Cuore Roma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Apa","sequence":"additional","affiliation":[{"name":"Dipartimento di Ostetricia e Ginecologia Universit\u00e0 Cattolica del Sacro Cuore Roma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. M.","family":"Fulghesu","sequence":"additional","affiliation":[{"name":"Dipartimento Chirurgico Materno\u2010Infantile e di Scienze delle Immagini Sezione di Clinica Ginecologica e Ostetrica e di Fisiopatologia della Riproduzione Umana Universit\u00e0 di Cagliari Cagliari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Lanzone","sequence":"additional","affiliation":[{"name":"OASI Institute for Research OASI \u2028S.Maria SS Troina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Morciano","sequence":"additional","affiliation":[{"name":"Dipartimento di Ostetricia e Ginecologia Universit\u00e0 Cattolica del Sacro Cuore Roma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Farcomeni","sequence":"additional","affiliation":[{"name":"Dipartimento di Sanit\u00e0 Pubblica e Malattie Infettive Universit\u00e0 di Roma \u201cSapienza\u201d Roma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. F.","family":"Gangale","sequence":"additional","affiliation":[{"name":"Dipartimento di Ostetricia e Ginecologia Universit\u00e0 Cattolica del Sacro Cuore Roma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Moro","sequence":"additional","affiliation":[{"name":"Dipartimento di Ostetricia e Ginecologia Universit\u00e0 Cattolica del Sacro Cuore Roma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Dipartimento di Ostetricia e Ginecologia Universit\u00e0 Cattolica del Sacro Cuore Roma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Ciardulli","sequence":"additional","affiliation":[{"name":"Dipartimento di Ostetricia e Ginecologia Universit\u00e0 Cattolica del Sacro Cuore Roma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Palla","sequence":"additional","affiliation":[{"name":"Dipartimento di Ostetricia e Ginecologia Universit\u00e0 Cattolica del Sacro Cuore Roma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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