| Genetic variation in P450c11AS in Chilean patients with low renin hypertension. | |
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MedLine Citation:
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PMID: 8954040 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Low renin hypertension (LRH), which accounts for 10-20% of patients with idiopathic "essential" hypertension, bears hormonal similarities to mineralocorticoid-induced hypertension, but elevated mineralocorticoid concentrations have not been found. Some patients with LRH have normal, rather than suppressed, plasma aldosterone concentrations, so that the ratio of aldosterone concentration to PRA (Aldo/PRA) is high, suggesting inappropriately increased aldosterone biosynthesis. We characterized the CYP11B2 gene that encodes the aldosterone synthase, P450c11AS, in hypertensive and control populations in a single clinic in Santiago, Chile. We directly sequenced the entire CYP11B2 gene in 12 patients with LRH, 2 high renin hypertensive controls, and 2 normotensive controls. All sequences were identical, except that 8 of 24 LRH alleles encoded arginine rather than lysine at position 173. The Arg173 and Lys173 variants were expressed in transfected MA-10 cells, and their ability to convert deoxycorticosterone to aldosterone was measured; the apparent Michaelis constant (Km) for Lys173 was 2.73 mumol/L; the Km for Arg173 was 2.53 mumol/L. The apparent maximal velocity (Vmax) for Lys173 was 6.5 x 10(-3) micrograms/mL.24 h; the Vmax for Arg173 was 7.8 x 10(-3) micrograms/mL.24 h. The first order rate constant, Vmax/Km was 2.38 for Lys173 and 3.08 for Arg173. As these values were not significantly different, we sought to determine whether Arg173 is a polymorphism linked to LRH. We examined position 173 in 52 unselected patients with idiopathic hypertension and 55 normotensive controls by PCR amplification of CYP11B2 exons 3-5 followed by digestion with Bsu361, which digests the Arg173 sequence, but not the Lys173 sequence. More of the hypertensive alleles (39 of 104, 37.5%) than normotensive alleles (25 of 110, 22.5%) carried Arg173 (chi 2 = 5.57; P < 0.02). Most of the Arg173 alleles (31 of 72, 43.1%) were from hypertensive patients with Aldo/PRA below 30, whereas only 5 of 24 (20.8%) Arg173 alleles were found in patients with Aldo/PRA greater than 30 (chi 2 = 3.79; P = 0.05) Thus, the ARg173 variant of CYP11B2 may be linked to LRH in Chilean patients. |
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Authors:
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C E Fardella; H Rodriguez; J Montero; G Zhang; P Vignolo; A Rojas; L Villarroel; W L Miller |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of clinical endocrinology and metabolism Volume: 81 ISSN: 0021-972X ISO Abbreviation: J. Clin. Endocrinol. Metab. Publication Date: 1996 Dec |
Date Detail:
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Created Date: 1997-01-06 Completed Date: 1997-01-06 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0375362 Medline TA: J Clin Endocrinol Metab Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 4347-51 Citation Subset: AIM; IM |
Affiliation:
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Department of Pediatrics, University of California, San Francisco 94143, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Aldosterone Synthase / genetics* Female Humans Hypertension / genetics* Male Middle Aged Mutation Polymerase Chain Reaction Renin / blood* |
| Grant Support | |
ID/Acronym/Agency:
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DK-37922/DK/NIDDK NIH HHS; DK-42154/DK/NIDDK NIH HHS; K11-DK-02123/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 1.14.15.4/Aldosterone Synthase; EC 3.4.23.15/Renin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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