{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:57:04Z","timestamp":1790035024973,"version":"4.0.1"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2006,9,20]],"date-time":"2006-09-20T00:00:00Z","timestamp":1158710400000},"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":[[2006,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Objective\u2002<\/jats:bold> We previously described an association between the \u2212344C\/T 5\u2032\u2010untranslated region (UTR) polymorphism in the CYP11B2 (aldosterone synthase) gene and hypertension with a raised aldosterone to renin ratio (ARR); the same genetic variant is also associated with impaired adrenal 11\u03b2\u2010hydroxylase efficiency. The \u2212344 polymorphism does not seem to be functional, so is likely to be in linkage with variants in CYP11B1 that determine the associated variation in 11\u03b2\u2010hydroxylase efficiency. We therefore aimed to determine whether there is an association between CYP11B1 variants and hypertension and\/or an altered ARR.<\/jats:p><jats:p><jats:bold>Design and measurements\u2002<\/jats:bold> We screened 160 subjects divided into four groups, normotensive controls, unselected hypertensive subjects, and hypertensive subjects with either a high (\u2265\u00a0750) or low ARR (\u2264\u00a0200), for variants in the coding region of CYP11B1 by single\u2010stranded conformation polymorphism (SSCP) and direct sequencing. The effects of these variants on enzyme function were assessed by conversion of 11\u2010deoxycortisol to cortisol and 11\u2010deoxycorticosterone (DOC) to corticosterone.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> Eight novel missense mutations were identified in the CYP11B1 gene that alter the encoded amino acids: R43Q, L83S, H125R, P135S, F139L, L158P, L186V and T196A. In each case they were heterozygous changes. However, no mutations were identified that could account for hypertension and\/or a raised ARR. The variants L158P and L83S severely impaired enzyme function while R43Q, F139L, P135S and T196A enzymes resulted in product levels that were approximately 30\u201350% that of wild\u2010type levels. The variant enzymes H125R and L186V resulted in substrate\u2010specific alterations in enzyme function. H125R decreased conversion of 11\u2010deoxycortisol to cortisol and L186V increased 11\u2010deoxycortisol conversion. Neither had an effect on the conversion of DOC to corticosterone.<\/jats:p><jats:p><jats:bold>Conclusion\u2002<\/jats:bold> No variants were identified in the coding region of CYP11B1 that could account for hypertension and\/or a raised ARR. However, this <jats:italic>in\u00a0vitro<\/jats:italic> study identifies the importance of these affected residues to enzyme function and will inform subsequent studies of structure\u2013function relationships.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2006.02673.x","type":"journal-article","created":{"date-parts":[[2006,9,20]],"date-time":"2006-09-20T14:33:57Z","timestamp":1158762837000},"page":"816-825","source":"Crossref","is-referenced-by-count":16,"title":["Functional effects of genetic variants in the 11\u03b2\u2010hydroxylase (CYP11B1) gene"],"prefix":"10.1111","volume":"65","author":[{"given":"Marianne","family":"Barr","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"MacKenzie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna M.","family":"Wilkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine D.","family":"Holloway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine C.","family":"Friel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"MacDonald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Fraser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M. 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