Apparent mineralocorticoid excess in a Brazilian kindred: hypertension in the heterozygote state
Apparent mineralocorticoid excess in a Brazilian kindred: hypertension in the heterozygote state
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巴西亲属明显盐皮质激素过量：杂合子状态下的高血压
DOI：
10.1097/00004872-199715120-00005
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发表时间：
1997
影响因子：
4.9
通讯作者：
P. Stewart
中科院分区：
文献类型：
--
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
Background Apparent mineralocorticoid excess (AME) is a cause of low-renin, low-aldosterone hypertension in which cortisol acts as a mineralocorticoid. The condition reflects an inability to inactivate cortisol to cortisone due to defective activity of the type 2 isozyme of 11b-hydroxysteroid dehydrogenase (11β-HSD2). Homozygous mutations in 11b-HSD2 gene in patients with AME have been described. A 7-year-old Brazilian girl had previously been found to have AME. Her father recently presented with mineralocorticoid hypertension at age 38 years. Objective To describe the clinical details, to perform steroid analyses and to assess the molecular basis for the hypertension in this kindred. Methods The 11βHSD2 gene was amplified from genomic DNA by the polymerase chain reaction and sequenced by direct chain-termination sequencing on an automatic DNA sequencer. The sequencing results were validated by restriction-site polymorphism. The mutant 11β-HSD2 protein was expressed in Chinese hamster ovary polyoma cells and enzymatic activity was assessed by metabolizing cortisol in vitro. Results Sequence analysis of genomic DNA revealed a novel C1061T point mutation in exon V of the human 11β-HSD2 gene, resulting in an amino acid substitution of alanine by valine at codon 328 of the enzyme protein (A328V). Expression studies confirmed that the mutant protein was devoid of 11β-HSD2 activity. A HhaI restriction-site polymorphism confirmed that the proband was homozygous for the mutation whereas both parents were heterozygotes. The father of the proband had hypertension, a normal serum potassium level, suppressed plasma renin activity and plasma aldosterone level and a moderately elevated urinary cortisol: cortisone metabolite ratio. Conclusions AME in this kindred is caused by a novel mutation in the 11β-HSD2 gene. Detection of hypokalaemia, at least in this kindred, is an insensitive screening test for mineralocorticoid-based hypertension. In contrast to results from previously investigated kindreds, we have demonstrated that this kindred has an abnormal phenotype in the heterozygote state. Further studies are now required in order to evaluate the role of 11β-HSD2 activity in the pathophysiology of ‘essential’ hypertension.
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盐皮质激素明显过量的家族中 HSD11B2 基因发生突变。
DOI：
10.1210/jcem.80.7.7608290
发表时间：
1995
期刊：
The Journal of clinical endocrinology and metabolism.
影响因子：
--
作者：
Wilson,RC;Krozowski,ZS;Li,K;Obeyesekere,VR;Razzaghy-Azar,M;Harbison,MD;Wei,JQ;Shackleton,CH;Funder,JW;New,MI
通讯作者：
New,MI
侧翼微卫星 11 β-羟基类固醇脱氢酶 2 型 (HSD11B2) 与黑人原发性高血压的遗传关联。
DOI：
10.1161/01.hyp.28.3.478
发表时间：
1996
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
WatsonJr,B;Bergman,SM;Myracle,A;Callen,DF;Acton,RT;Warnock,DG
通讯作者：
Warnock,DG
影响因子：
4.4
作者：
AGARWAL, AK;ROGERSON, FM;WHITE, PC
通讯作者：
WHITE, PC
影响因子：
15.9
作者：
STEWART, PM;CORRIE, JET;EDWARDS, CRW
通讯作者：
EDWARDS, CRW
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