更新于：2024-11-01

Hypercholesterolemia, Autosomal Dominant, 3

常染色体显性遗传性高胆固醇血症3型

更新于：2024-11-01

基本信息

别名

FH3、FHCL3、HCHOLA3

+ [4]

简介-

关联

项与常染色体显性遗传性高胆固醇血症3型相关的药物

Recaticimab

瑞卡西单抗

靶点

PCSK9

作用机制

PCSK9抑制剂

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段申请上市

首次获批国家/地区-

首次获批日期1800-01-20

项与常染色体显性遗传性高胆固醇血症3型相关的临床试验

NCT04844125 / Completed临床3期

A Multicentric, Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate the Efficacy and Safety of SHR-1209 in Patients With Hypercholesterolemia

This study is ongoing to evaluate the efficacy and safety of SHR-1209 in patients with hypercholesterolemia.

开始日期2021-04-14

申办/合作机构

江苏恒瑞医药股份有限公司

NCT04656028 / RecruitingN/AIIT

Impact of Genetic Testing and Motivational Counseling on the Adherence to Healthy Lifestyle and Hypolipidemic Therapy and Efficiency of Cascade Screening in Patients With Familial Hypercholesterolemia (GENMOTIV-FH)

To date, there are highly effective lipid-lowering drugs, the combination of which makes it possible to achieve the target level of LDL-C in most patients with familial hypercholesterolemia (FH). However, the effectiveness of treatment of FH patients strongly depends on adherence to lipid-lowering therapy and to the healthy lifestyle, as well as the detection of the disease and the therapy prescription as early as possible, better in childhood. The aim of the study is to assess the impact of genetic testing and motivational counseling on the effectiveness of treatment and cascade screening in patients with FH.

开始日期2020-06-15

申办/合作机构

National Medical Research Center for Therapy and Preventive Medicine

[+1]

100 项与常染色体显性遗传性高胆固醇血症3型相关的临床结果

登录后查看更多信息

100 项与常染色体显性遗传性高胆固醇血症3型相关的转化医学

登录后查看更多信息

0 项与常染色体显性遗传性高胆固醇血症3型相关的专利（医药）

登录后查看更多信息

项与常染色体显性遗传性高胆固醇血症3型相关的文献（医药）

2017-01-01·Molecular and Cellular Endocrinology2区 · 医学

Disordered zonal and cellular CYP11B2 enzyme expression in familial hyperaldosteronism type 3

2区 · 医学

Article

作者: Hironobu Sasano ; Martin O. Bohlen ; Xin Qi ; Elise P. Gomez-Sanchez ; Celso E. Gomez-Sanchez ; Max Wisgerhof

Three forms of familial primary aldosteronism have been recognized. Familial Hyperaldosteronism type 1 (FH1) or dexamethasone suppressible hyperaldosteronism, FH2, the most common form of as yet unknown cause(s), and FH3. FH3 is due to activating mutations of the potassium channel gene KCNJ5 that increase constitutive and angiotensin II-induced aldosterone synthesis. In this study we examined the cellular distribution of CYP11B2, CYP11B1, CYP17A1 and KCNJ5 in adrenals from two FH3 siblings using immunohistochemistry and immunofluorescence and obtained unexpected results. The adrenals were markedly enlarged with loss of zonation. CYP11B2 was expressed sporadically throughout the adrenal cortex. CYP11B2 was most often expressed by itself, relatively frequently with CYP17A1, and less frequently with CYP11B1. KCNJ5 was co-expressed with CYP11B2 and in some cells with CYP11B1. This aberrant co-expression of enzymes likely explains the abnormally high secretion rate of the hybrid steroid, 18-oxocortisol.

2015-02-01·Journal of Endocrinology3区 · 医学

An update on novel mechanisms of primary aldosteronism

3区 · 医学

Review

作者: Boulkroun, Sheerazed ; Fernandes-Rosa, Fabio ; Zennaro, Maria-Christina

Primary aldosteronism (PA) is the most common and curable form of secondary hypertension. It is caused in the majority of cases by either unilateral aldosterone overproduction due to an aldosterone-producing adenoma (APA) or by bilateral adrenal hyperplasia. Recent advances in genome technology have allowed researchers to unravel part of the genetic abnormalities underlying the development of APA and familial hyperaldosteronism. Recurrent somatic mutations in genes coding for ion channels (KCNJ5 and CACNA1D) and ATPases (ATP1A1 and ATP2B3) regulating intracellular ionic homeostasis and cell membrane potential have been identified in APA. Similar germline mutations of KCNJ5 were identified in a severe familial form of PA, familial hyperaldosteronism type 3 (FH3), whereas de novo germline CACNA1D mutations were found in two cases of hyperaldosteronism associated with a complex neurological disorder. These results have allowed a pathophysiological model of APA development to be established. This model involves modifications in intracellular ionic homeostasis and membrane potential, accounting for ∼50% of all tumors, associated with specific gender differences and severity of PA. In this review, we describe the different genetic abnormalities associated with PA and discuss the mechanisms whereby they lead to increased aldosterone production and cell proliferation. We also address some of the foreseeable consequences that genetic knowledge may contribute to improve diagnosis and patient care.

2014-01-01·Cardiovascular Issues in Endocrinology4区 · 医学

Genetics of Primary Aldosteronism

4区 · 医学

Article

作者: Funder, John W

Primary aldosteronism (PA) accounts for ∼10% of hypertension, which is commonly caused by an aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia. Germline mutations producing PA are considered rare and termed familial hyperaldosteronism (FH) [1, 2, 3]. Since early 2011, a series of somatic mutations confined to the adrenal cortex has been reported, accounting for about half of APA. These mutations are in genes encoding components of the Kir 3.4 (GIRK4) potassium channel (KCNJ5), sodium/potassium and calcium ATPases (ATP1A1 and ATP2B3) and a voltage-dependent C-type calcium channel (CACNA1D). FH-1 (glucocorticoid-remediable hyperaldosteronism) results from a chimeric gene (5'-end of CYP11B1 fused to 3'-end of CYP11B2) and accounts for ∼1% of PA. FH-3 is very rare, is caused by bilateral expression of mutant KCNJ5 and usually results in florid hyperaldosteronism requiring early bilateral adrenalectomy. FH-2 is the most common form of hereditary PA (2 first-degree relatives with either an APA or bilateral adrenal hyperplasia) and currently thought to represent ∼6% of PA; the true prevalence may be considerably higher. The mutation(s) causing FH-2 are unknown but appear dominant, as is the case for FH-1 and FH-3. No studies have been done on possible recessive forms of PA.