Evidence map›Paper›PMID 33112806›Full record

ArticleEndocrine-related cancer2021

Phosphodiesterase 2A and 3B variants are associated with primary aldosteronism.

Marcela Rassi-Cruz, Andrea G Maria, Fabio R Faucz, Edra London, Leticia A P Vilela, Lucas S Santana, Anna Flavia F Benedetti, Tatiana S Goldbaum, Fabio Y Tanno, Vitor Srougi and 14 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Endocrine-related cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.1field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 19 citations in OpenAlex.

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  8. Genetics of Primary Aldosteronism.Hypertension (Dallas, Tex. : 1979) · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 3 institutions in 2 countries.

Marcela Rassi-CruzUnidade de Suprarrenal, Laboratório de Hormônios e Genética Molecular LIM/42, Serviço de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Andrea G MariaSection on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland, USA.
Fabio R FauczSection on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland, USA.ORCID 0000-0001-7959-9842
Edra LondonSection on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland, USA.
Leticia A P VilelaUnidade de Suprarrenal, Laboratório de Hormônios e Genética Molecular LIM/42, Serviço de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Lucas S SantanaUnidade de Suprarrenal, Laboratório de Hormônios e Genética Molecular LIM/42, Serviço de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Anna Flavia F BenedettiUnidade de Suprarrenal, Laboratório de Hormônios e Genética Molecular LIM/42, Serviço de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Tatiana S GoldbaumUnidade de Suprarrenal, Laboratório de Hormônios e Genética Molecular LIM/42, Serviço de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Fabio Y TannoServiço de Urologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.ORCID 0000-0001-7959-9842
Vitor SrougiServiço de Urologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Jose L ChamboServiço de Urologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Maria Adelaide A PereiraUnidade de Suprarrenal, Laboratório de Hormônios e Genética Molecular LIM/42, Serviço de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Aline C B S CavalcanteInstituto de Radiologia InRad, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Francisco C CarnevaleInstituto de Radiologia InRad, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Bruna PilanInstituto de Radiologia InRad, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Luiz A BortolottoUnidade de Hipertensão, Instituto do Coração (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Luciano F DragerUnidade de Hipertensão, Instituto do Coração (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Antonio M LerarioUnidade de Suprarrenal, Laboratório de Hormônios e Genética Molecular LIM/42, Serviço de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Ana Claudia LatronicoUnidade de Suprarrenal, Laboratório de Hormônios e Genética Molecular LIM/42, Serviço de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Maria Candida B V FragosoUnidade de Suprarrenal, Laboratório de Hormônios e Genética Molecular LIM/42, Serviço de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Berenice B MendoncaUnidade de Suprarrenal, Laboratório de Hormônios e Genética Molecular LIM/42, Serviço de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Maria Claudia N ZerbiniDivisão de Anatomia Patológica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Constantine A StratakisSection on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland, USA.
Madson Q AlmeidaUnidade de Suprarrenal, Laboratório de Hormônios e Genética Molecular LIM/42, Serviço de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo · BREunice Kennedy Shriver National Institute of Child Health and Human Development · USNational Institutes of Health · US

Funding

Molecular Genetics of Endocrine Tumors and Related DisordersZIAHD008920 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI STRATAKIS, CONSTANTINE A. · 2012 to 2021
$25.8M
Endocrine-immune reproductive system interactionsZ01HD008720 · NICHD · CHILD HEALTH AND HUMAN DEVELOPMENT · PI CHROUSOS, GEORGE P · 2000 to 2000
–
Intramural NIH HHS Z01 HD008720Intramural NIH HHS ZIA HD008920
6 · The paper itself

Abstract

Familial primary aldosteronism (PA) is rare and mostly diagnosed in early-onset hypertension (HT). However, 'sporadic' bilateral adrenal hyperplasia (BAH) is the most frequent cause of PA and remains without genetic etiology in most cases. Our aim was to investigate new genetic defects associated with BAH and PA. We performed whole-exome sequencing (paired blood and adrenal tissue) in six patients with PA caused by BAH that underwent unilateral adrenalectomy. Additionally, we conducted functional studies in adrenal hyperplastic tissue and transfected cells to confirm the pathogenicity of the identified genetic variants. Rare germline variants in phosphodiesterase 2A (PDE2A) and 3B (PDE3B) genes were identified in three patients. The PDE2A heterozygous variant (p.Ile629Val) was identified in a patient with BAH and early-onset HT at 13 years of age. Two PDE3B heterozygous variants (p.Arg217Gln and p.Gly392Val) were identified in patients with BAH and HT diagnosed at 18 and 33 years of age, respectively. A strong PDE2A staining was found in all cases of BAH in zona glomerulosa and/or micronodules (that were also positive for CYP11B2). PKA activity in frozen tissue was significantly higher in BAH from patients harboring PDE2A and PDE3B variants. PDE2A and PDE3B variants significantly reduced protein expression in mutant transfected cells compared to WT. Interestingly, PDE2A and PDE3B variants increased SGK1 and SCNN1G/ENaCg at mRNA or protein levels. In conclusion, PDE2A and PDE3B variants were associated with PA caused by BAH. These novel genetic findings expand the spectrum of genetic etiologies of PA.

Indexed as

AdolescentAdultAgedCyclic Nucleotide Phosphodiesterases, Type 2Cyclic Nucleotide Phosphodiesterases, Type 3FemaleHumansHyperaldosteronismMaleMiddle AgedCyclic Nucleotide Phosphodiesterases, Type 2Cyclic Nucleotide Phosphodiesterases, Type 3PDE2A protein, humanPDE3B protein, humanadrenal hyperplasiaphosphodiesterasesprimary aldosteronism

Identifiers

PMID33112806
PMCPMC7757641
OpenAlexW3093979855

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.