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Serum progesterone was detected with liquid chromatography-tandem mass spectrometry. DNA methylation of <jats:italic>SOCS3<\/jats:italic> was determined by MethylTarget\u2122. Linear regression was applied to evaluate the associations of progesterone and <jats:italic>SOCS3<\/jats:italic> methylation with marks of glucose metabolism. Logistic regression was employed to investigate the independent and combined effects of progesterone and <jats:italic>SOCS3<\/jats:italic> methylation with T2DM in men and postmenopausal women.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>After multiple adjustment, progesterone was positively associated with T2DM in both men (odds ratio (OR) (95% confidence interval (CI)): 2.77 (1.79, 4.29)) and postmenopausal women (OR (95% CI): 1.85 (1.26, 2.72)). Methylation level of <jats:italic>Chr17:76,356,190<\/jats:italic> or <jats:italic>Chr17:76,356,199<\/jats:italic> (<jats:italic>SOCS3<\/jats:italic>) was negatively associated with T2DM in both men (OR (95% CI): 0.58 (0.39, 0.86) or 0.27 (0.14, 0.51)) and postmenopausal women (OR (95% CI): 0.43 (0.29, 0.65) or 0.53 (0.28, 0.99)). Subjects with high progesterone and low <jats:italic>Chr17:76,356,190<\/jats:italic> or <jats:italic>Chr17:76,356,199<\/jats:italic> methylation were more susceptible to have a higher prevalence of T2DM (men: OR (95% CI): 5.20 (2.49, 10.85) or 5.62 (2.74, 11.54); postmenopausal women: OR (95% CI): 3.66 (1.85, 7.26) or 3.27 (1.66, 6.45)).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The independent and combined effects of progesterone and <jats:italic>SOCS3<\/jats:italic> methylation on T2DM were found among men and postmenopausal women, suggesting that ensuring low levels of progesterone and high methylation of <jats:italic>SOCS3<\/jats:italic> could reduce the prevalence of T2DM.<\/jats:p>\n                <jats:p><jats:bold>Trial registration<\/jats:bold> The Chinese Clinical Trial registration: The Henan Rural Cohort Study, ChiCTR-OOC-15006699. Registered 06 July 2015, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.chictr.org.cn\/showproj.aspx?proj=11375\">http:\/\/www.chictr.org.cn\/showproj.aspx?proj=11375<\/jats:ext-link><\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13148-021-01172-9","type":"journal-article","created":{"date-parts":[[2021,9,26]],"date-time":"2021-09-26T19:04:33Z","timestamp":1632683073000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Combined effects of progesterone and SOCS3 DNA methylation on T2DM: a case\u2013control study"],"prefix":"10.1186","volume":"13","author":[{"given":"Lulu","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenxing","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaotian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dandan","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengling","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luting","family":"Nie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keliang","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingqing","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Jing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjie","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chongjian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7898-093X","authenticated-orcid":false,"given":"Wenqian","family":"Huo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,9,26]]},"reference":[{"key":"1172_CR1","doi-asserted-by":"publisher","first-page":"965243","DOI":"10.5402\/2012\/965243","volume":"2012","author":"A Shankar","year":"2012","unstructured":"Shankar A, Teppala S, Sabanayagam C. 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