{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T10:00:16Z","timestamp":1760781616233},"reference-count":34,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Regeneration of active glucocorticoids within liver and adipose tissue by the enzyme 11\u03b2-hydroxysteroid dehydrogenase type 1 (11\u03b2-HSD1) may be of pathophysiological importance in obesity and metabolic syndrome and is a therapeutic target in type 2 diabetes. Polymorphisms in HSD11B1, the gene encoding 11\u03b2-HSD1, have been associated with metabolic phenotype in humans, including type 2 diabetes and hypertension. Here, we have tested the functional consequences of two single nucleotide polymorphisms located in contexts that potentially affect tissue levels of 11\u03b2-HSD1. We report no effect of allelic variation at rs846910, a polymorphism within the 5\u2032-flanking region of the gene on HSD11B1 promoter activity in vitro. However, compared with the common G allele, the A allele of rs13306421, a polymorphism located two nucleotides 5\u2032 to the translation initiation site, gave higher 11\u03b2-HSD1 expression and activity in vitro and was translated at higher levels in in vitro translation reactions, possibly associated with a lower frequency of \u201cleaky scanning.\u201d These data suggest that this polymorphism may have direct functional consequences on levels of 11\u03b2-HSD1 enzyme activity in vivo. However, the rs13306421 A sequence variant originally reported in other ethnic groups may be of low prevalence because it was not detected in a population of 600 European Caucasian women.<\/jats:p>","DOI":"10.1210\/en.2009-0663","type":"journal-article","created":{"date-parts":[[2009,11,25]],"date-time":"2009-11-25T04:57:09Z","timestamp":1259125029000},"page":"195-202","source":"Crossref","is-referenced-by-count":20,"title":["Functional Effects of Polymorphisms in the Human Gene Encoding 11\u03b2-Hydroxysteroid Dehydrogenase Type 1 (11\u03b2-HSD1): A Sequence Variant at the Translation Start of 11\u03b2-HSD1 Alters Enzyme Levels"],"prefix":"10.1210","volume":"151","author":[{"given":"Elise L. V.","family":"Malavasi","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Science (E.L.V.M., V.K., N.N., R.S.D., B.R.W., K.E.C.), Queen\u2019s Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"},{"name":"Division of Endocrinology (E.L.V.M., A.G., U.P., R.P.), Department of Clinical Medicine, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Val","family":"Kelly","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science (E.L.V.M., V.K., N.N., R.S.D., B.R.W., K.E.C.), Queen\u2019s Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikita","family":"Nath","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science (E.L.V.M., V.K., N.N., R.S.D., B.R.W., K.E.C.), Queen\u2019s Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Gambineri","sequence":"additional","affiliation":[{"name":"Division of Endocrinology (E.L.V.M., A.G., U.P., R.P.), Department of Clinical Medicine, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel S.","family":"Dakin","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science (E.L.V.M., V.K., N.N., R.S.D., B.R.W., K.E.C.), Queen\u2019s Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uberto","family":"Pagotto","sequence":"additional","affiliation":[{"name":"Division of Endocrinology (E.L.V.M., A.G., U.P., R.P.), Department of Clinical Medicine, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renato","family":"Pasquali","sequence":"additional","affiliation":[{"name":"Division of Endocrinology (E.L.V.M., A.G., U.P., R.P.), Department of Clinical Medicine, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian R.","family":"Walker","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science (E.L.V.M., V.K., N.N., R.S.D., B.R.W., K.E.C.), Queen\u2019s Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen E.","family":"Chapman","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science (E.L.V.M., V.K., N.N., R.S.D., B.R.W., K.E.C.), Queen\u2019s Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071614112649000_R1","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1210\/er.2003-0031","article-title":"11\u03b2-Hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response.","volume":"25","author":"Tomlinson","year":"2004","journal-title":"Endocr Rev"},{"key":"2020071614112649000_R2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S002966510700523X","article-title":"Extra-adrenal regeneration of glucocorticoids by 11\u03b2-hydroxysteroid dehydrogenase type 1: physiological regulator and pharmacological target for energy partitioning.","volume":"66","author":"Walker","year":"2007","journal-title":"Proc Nutr Soc"},{"key":"2020071614112649000_R3","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1210\/rp.59.1.359","article-title":"Glucocorticoids and 11\u03b2-hydroxysteroid dehydrogenase in adipose tissue.","volume":"59","author":"Seckl","year":"2004","journal-title":"Recent Prog Horm Res"},{"key":"2020071614112649000_R4","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1038\/oby.2007.618","article-title":"Omental 11\u03b2-hydroxysteroid dehydrogenase 1 correlates with fat cell size independently of obesity.","volume":"15","author":"Michailidou","year":"2007","journal-title":"Obesity"},{"key":"2020071614112649000_R5","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1126\/science.1066285","article-title":"A transgenic model of visceral obesity and the metabolic syndrome.","volume":"294","author":"Masuzaki","year":"2001","journal-title":"Science"},{"key":"2020071614112649000_R6","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1172\/JCI17845","article-title":"Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in mice.","volume":"112","author":"Masuzaki","year":"2003","journal-title":"J Clin Invest"},{"key":"2020071614112649000_R7","doi-asserted-by":"crossref","first-page":"7088","DOI":"10.1073\/pnas.0305524101","article-title":"Metabolic syndrome without obesity: hepatic overexpression of 11\u03b2-hydroxysteroid dehydrogenase type 1 in transgenic 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