Progress on Genetic Basis of Primary Aldosteronism
Abstract
:1. Introduction
2. Genetic Basis of PA
2.1. Familial Hyperaldosteronism
2.1.1. FA Type I
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- PA diagnosed at a young age (before the age of 30);
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- A positive family history of PA;
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- Family members with a history of cerebrovascular accidents at an early age [13].
2.1.2. FA Type II
- -
- Finding FA in at least two relatives of a PA patient;
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- Exclusion of type I FA.
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- AT1 encoding type 1 angiotensin II receptor isoform, which has a vasopressor effect and regulates aldosterone secretion;
- -
- CYP11B2 encoding aldosterone synthase;
- -
- MEN1 encoding menin 1, which functions as a transcriptional regulator;
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- RBaK encoding RB-associated KRAB zinc finger protein; this gene encodes a nuclear protein which interacts with the tumor suppressor retinoblastoma 1 (this protein contains a Kruppel-associated box (KRAB), which is a transcriptional repressor motif);
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- PMS2 encoding mismatch repair endonuclease PMS2 (Postmeiotic Segregation Increased 2);
- -
- GNA12 encoding guanine nucleotide-binding protein (G protein) subunit alpha 12, which is involved as a modulator or transducer in various transmembrane signaling systems.
2.1.3. FA Type III
2.1.4. FA Type IV
2.2. Mutations in APA and BAH
2.2.1. KCNJ5
2.2.2. CACNA1D
2.2.3. ATP1A1 and ATP2B3
2.2.4. ARMC5
2.2.5. CTNNB1
2.2.6. mTORC1, EVs and Other Area of Active Investigation
2.3. Aldosterone-Producing Cell Clusters
3. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Patients with sustained blood pressure above 160–179/100–109 mmHg) or systolic blood pressure above >180/110 mmHg |
Patients with resistant HT (blood pressure not controlled by three conventional drugs including a diuretic) or controlled BP (<140/90 mmHg) on four or more antihypertensive drugs |
Patients with HT and spontaneous or diuretic-induced hypokalemia |
Patients with HT and an adrenal incidentaloma |
Patients with HT and a family history of early-onset hypertension or cerebrovascular accident at a young age (<40 years) |
All first-degree relatives of patients with PA |
Patients with HT and sleep apnea |
FA Type I | FA Type II | FA Type III | FA Type IV | |
---|---|---|---|---|
Transmission | AD | AD | AD | AD or de novo |
Gene | Chimeric CYP11B1/B2 | CLCN2 | KCNJ5 | CACNA1H |
Protein | Aldosterone synthase | Not known | GIRK4 | Cav3.2 |
Biological effect | Aldosterone synthase inducible by ACTH stimulation | Increased Cl- efflux | Reduced K+ selectivity and increased Na+ influx | Increased Ca2+ entry |
Age at symptom onset | Often <20 years | Variable, often <20 years | Variable, often <20 years | <10 years |
PA in relatives | Yes | Yes | <20 years (variable in moderate forms) | Yes/no |
Particular characteristics | Familiar history of stroke <40 years, hybrid steroids in urine, BAH | APA/BAH | BAH | Not described |
Severity of hypertension | Normal or resistant | Normal or resistant | Extremely severe | Normal or severe |
Hypokalemia | Yes/no | Yes/no | Very often in severe forms | Yes/no |
Aldosterone level | Normal or high | Normal or high | Very high | Normal or high |
Therapy | Glucocorticoids, MRAs | MRAs, adrenalectomy | MRAs, bilateral adrenalectomy | Not standardized, likely positive effect ofcalcium chanel blockers |
Genetic Variant | Prevalence (%) | Affected Protein |
---|---|---|
KCNJ5 | 43% | GIRK4 |
CACNA1D | 21% | Cav 1.3 |
ATP1A1 | 17% | ATPase Na+/K+ transporting subunit alpha 1 |
ATP2B3 | unknown | ATPase plasma membrane Ca2+ transporting 3 |
CACNA1H | unknown | Cav 3.2 |
ARMC5 | unknown | Aarmadillo repeat containing 5 |
CTNNB1 | unknown | Catenin beta 1 |
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Karwacka, I.; Obołończyk, Ł.; Kaniuka-Jakubowska, S.; Bohdan, M.; Sworczak, K. Progress on Genetic Basis of Primary Aldosteronism. Biomedicines 2021, 9, 1708. https://doi.org/10.3390/biomedicines9111708
Karwacka I, Obołończyk Ł, Kaniuka-Jakubowska S, Bohdan M, Sworczak K. Progress on Genetic Basis of Primary Aldosteronism. Biomedicines. 2021; 9(11):1708. https://doi.org/10.3390/biomedicines9111708
Chicago/Turabian StyleKarwacka, Izabela, Łukasz Obołończyk, Sonia Kaniuka-Jakubowska, Michał Bohdan, and Krzysztof Sworczak. 2021. "Progress on Genetic Basis of Primary Aldosteronism" Biomedicines 9, no. 11: 1708. https://doi.org/10.3390/biomedicines9111708
APA StyleKarwacka, I., Obołończyk, Ł., Kaniuka-Jakubowska, S., Bohdan, M., & Sworczak, K. (2021). Progress on Genetic Basis of Primary Aldosteronism. Biomedicines, 9(11), 1708. https://doi.org/10.3390/biomedicines9111708