Mutants of 11beta-hydroxysteroid dehydrogenase (11-HSD2) with partial activity: improved correlations between genotype and biochemical phenotype in apparent mineralocorticoid excess.
Mutants of 11beta-hydroxysteroid dehydrogenase (11-HSD2) with partial activity: improved correlations between genotype and biochemical phenotype in apparent mineralocorticoid excess.
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具有部分活性的 11β-羟基类固醇脱氢酶 (11-HSD2) 突变体：改善明显盐皮质激素过量时基因型和生化表型之间的相关性。
DOI：
10.1161/01.hyp.34.4.638
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
White,PC
中科院分区：
文献类型：
--
作者：
Nunez,BS;Rogerson,FM;Mune,T;Igarashi,Y;Nakagawa,Y;Phillipov,G;Moudgil,A;Travis,LB;Palermo,M;Shackleton,C;White,PC
—Mutations in the kidney isozyme of human 11-hydroxysteroid dehydrogenase (11-HSD2) cause apparent mineralocorticoid excess, an autosomal recessive form of familial hypertension. We studied 4 patients with AME, identifying 4 novel and 3 previously reported mutations in theHSD11B2(HSD11K) gene. Point mutations causing amino acid substitutions were introduced into a pCMV5/11HSD2 expression construct and expressed in mammalian CHOP cells. Mutations L179R and R208H abolished activity in whole cells. Mutants S180F, A237V, and A328V had 19%, 72%, and 25%, respectively, of the activity of the wild-type enzyme in whole cells when cortisol was used as the substrate and 80%, 140%, and 55%, respectively, of wild-type activity when corticosterone was used as the substrate. However, these mutant proteins were only 0.6% to 5.7% as active as the wild-type enzyme in cell lysates, suggesting that these mutations alter stability of the enzyme. In regression analyses of all AME patients with published genotypes, several biochemical and clinical parameters were highly correlated with mutant enzymatic activity, demonstrated in whole cells, when cortisol was used as the substrate. These included the ratio of urinary cortisone to cortisol metabolites (R2=0.648,P<0.0001), age at presentation (R2=0.614,P<0.0001), and birth weight (R2=0.576,P=0.0004). Approximately 5% conversion of cortisol to cortisone is predicted in subjects with mutations that completely inactivate HSD11B2, suggesting that a low level of enzymatic activity is mediated by another enzyme, possibly 11-HSD1.
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地塞米松反应性盐皮质激素过量所致皮质醇和皮质酮代谢异常的研究（作者译）。
DOI：
10.1507/endocrine1927.55.10_1341
发表时间：
1979
期刊：
Nihon Naibunpi Gakkai zasshi
影响因子：
--
作者：
Y. Igarashi;S. Egi;A. Takehiro;T. Ohzeki;H. Kawaguchi
通讯作者：
H. Kawaguchi
巴西亲属明显盐皮质激素过量：杂合子状态下的高血压
影响因子：
4.9
作者：
A. Li;Kevin X. Z. Li;S. Marui;Z. Krozowski;M. C. Batista;C. Whorwood;I. J. Arnhold;C. Shackleton;B. Mendonca;P. Stewart
通讯作者：
P. Stewart
影响因子：
4.4
作者：
AGARWAL, AK;ROGERSON, FM;WHITE, PC
通讯作者：
WHITE, PC
表观盐皮质激素过量：基因型与生化表型相关。
DOI：
10.1161/01.hyp.27.6.1193
发表时间：
1996
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Mune,T;White,PC
通讯作者：
White,PC
影响因子：
9.8
作者：
Li, A;Tedde, R;Stewart, PM
通讯作者：
Stewart, PM