Evidence map›Paper›PMID 38851835›Full record

ArticleScientific reports2024

Discovery of RXFP2 genetic association in resistant hypertensive men and RXFP2 antagonists for the treatment of resistant hypertension.

Shan-Shan Zhang, Lance Larrabee, Andrew H Chang, Sapna Desai, Lisa Sloan, Xin Wang, Yixuan Wu, Nazia Parvez, Karen Amaratunga, Allison C Hartman and 20 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors.

Shan-Shan Zhang *Therapeutics Division, 23andMe, 349 Oyster Point Blvd, South San Francisco, CA, 94080, USA.
Lance Larrabee *Therapeutics Division, 23andMe, 349 Oyster Point Blvd, South San Francisco, CA, 94080, USA.
Andrew H ChangTherapeutics Division, 23andMe, 349 Oyster Point Blvd, South San Francisco, CA, 94080, USA.
Sapna DesaiMedicinal Science and Technology, GSK, Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, UK.
Lisa SloanMedicinal Science and Technology, GSK, Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, UK.
Xin WangResearch, 23andMe, 223 N Mathilda Ave., Sunnyvale, CA, 94086, USA.ORCID https://orcid.org/0000-0001-7242-357X
Yixuan WuTherapeutics Division, 23andMe, 349 Oyster Point Blvd, South San Francisco, CA, 94080, USA.
Nazia ParvezMedicinal Science and Technology, GSK, Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, UK.
Karen AmaratungaMedicinal Science and Technology, GSK, Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, UK.
Allison C HartmanMedicinal Science and Technology, GSK, 1250 S. Collegeville Rd., Collegeville, PA, 19426, USA.
Abby WhitnallMedicinal Science and Technology, GSK, Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, UK.
Joseph MasonMedicinal Science and Technology, GSK, Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, UK.
Nicholas P BartonMedicinal Science and Technology, GSK, Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, UK.
Audrey Y ChuGenomic Sciences, GSK, 300 Technology Square, Cambridge, MA, 02139, USA.
Jonathan M DavitteGenomic Sciences, GSK, 300 Technology Square, Cambridge, MA, 02139, USA.
Adam J CsakaiMedicinal Science and Technology, GSK, 200 Cambridgepark Drive, Cambridge, MA, 02140, USA.
Caitlin Vestal TibbettsMedicinal Science and Technology, GSK, 200 Cambridgepark Drive, Cambridge, MA, 02140, USA.
Audrey E TolbertMedicinal Science and Technology, GSK, 200 Cambridgepark Drive, Cambridge, MA, 02140, USA.
Heather O'KeefeMedicinal Science and Technology, GSK, 200 Cambridgepark Drive, Cambridge, MA, 02140, USA.
Jessie PolancoTherapeutics Division, 23andMe, 349 Oyster Point Blvd, South San Francisco, CA, 94080, USA.
Joseph FoleyNovel Human Genetics Research Unit, GSK, 1250 S. Collegeville Rd., Collegeville, PA, 19426, USA.
Casey KmettDMPK, GSK, 1250 S. Collegeville Rd, Collegeville, PA, 19426, USA.
Jonathan KehlerBioanalysis, Immunogenicity and Biomarkers, GSK, 1250 S. Collegeville Rd., Collegeville, PA, 19426, USA.
Gabriela KozejovaMedicinal Science and Technology, GSK, Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, UK.
Feng WangDMPK, GSK, 1250 S. Collegeville Rd, Collegeville, PA, 19426, USA.
Andrew P MayerBioanalysis, Immunogenicity and Biomarkers, GSK, 1250 S. Collegeville Rd., Collegeville, PA, 19426, USA.
Patrick KoenigTherapeutics Division, 23andMe, 349 Oyster Point Blvd, South San Francisco, CA, 94080, USA.
Davide FolettiTherapeutics Division, 23andMe, 349 Oyster Point Blvd, South San Francisco, CA, 94080, USA.
Steven J PittsResearch, 23andMe, 223 N Mathilda Ave., Sunnyvale, CA, 94086, USA.ORCID https://orcid.org/0000-0002-9673-7394
Christine G SchnackenbergNovel Human Genetics Research Unit, GSK, 1250 S. Collegeville Rd., Collegeville, PA, 19426, USA. Christine.G.Schnackenberg@gsk.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hypertension remains a leading cause of cardiovascular and kidney diseases. Failure to control blood pressure with ≥ 3 medications or control requiring ≥ 4 medications is classified as resistant hypertension (rHTN) and new therapies are needed to reduce the resulting increased risk of morbidity and mortality. Here, we report genetic evidence that relaxin family peptide receptor 2 (RXFP2) is associated with rHTN in men, but not in women. This study shows that adrenal gland gene expression of RXFP2 is increased in men with hypertension and the RXFP2 natural ligand, INSL3, increases adrenal steroidogenesis and corticosteroid secretion in human adrenal cells. To address the hypothesis that RXFP2 activation is an important mechanism in rHTN, we discovered and characterized small molecule and monoclonal antibody (mAb) blockers of RXFP2. The novel chemical entities and mAbs show potent, selective inhibition of RXFP2 and reduce aldosterone and cortisol synthesis and release. The RXFP2 mAbs have suitable rat pharmacokinetic profiles to evaluate the role of RXFP2 in the development and maintenance of rHTN. Overall, we identified RXFP2 activity as a potential new mechanism in rHTN and discovered RXFP2 antagonists for the future interrogation of RXFP2 in cardiovascular and renal diseases.

Indexed as

HypertensionReceptors, G-Protein-CoupledReceptors, PeptideAdrenal GlandsAldosteroneAnimalsAntibodies, MonoclonalAntihypertensive AgentsDrug ResistanceFemaleHumansMaleRatsAldosteroneAntibodies, MonoclonalAntihypertensive AgentsReceptors, G-Protein-CoupledReceptors, PeptideRXFP2 protein, human

Identifiers

PMID38851835
PMCPMC11162469

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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.