ArticleThe Journal of clinical investigation2017
Blood pressure-associated polymorphism controls ARHGAP42 expression via serum response factor DNA binding.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- Revealing the Shared Genetic Architecture of Metabolic Dysfunction-Associated Steatotic Liver Disease-Related Traits Through Genomic Structural Equation Modeling.Genetic epidemiology · 2026Article
- Epigenetic alteration of smooth muscle cells regulates endothelin-dependent blood pressure and hypertensive arterial remodeling.The Journal of clinical investigation · 2025Article
- Uncovering therapeutic targets for Pre-eclampsia and pregnancy hypertension via multi-tissue data integration.BMC pregnancy and childbirth · 2025Article
- Gene editing of angiotensin for blood pressure management.International journal of cardiology. Cardiovascular risk and prevention · 2024Article
- Serum response factor promoting axonal regeneration by activating the Ras-Raf-Cofilin signaling pathway after the spinal cord injury.CNS neuroscience & therapeutics · 2024Article
- Deciphering the causal relationship between blood pressure and regional white matter integrity: A two-sample Mendelian randomization study.Journal of neuroscience research · 2023Article
- Semaphorin3A Exacerbates Cardiac Microvascular Rarefaction in Pressure Overload-Induced Heart Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Prdm6 drives ductus arteriosus closure by promoting ductus arteriosus smooth muscle cell identity and contractility.JCI insight · 2023Article
- A Single Nucleotide Polymorphism inCirculation research · 2022Article
- Unfolding the genotype-to-phenotype black box of cardiovascular diseases through cross-scale modeling.iScience · 2022Article
- Redefining tissue specificity of genetic regulation of gene expression in the presence of allelic heterogeneity.American journal of human genetics · 2022Article
- The actin depolymerizing factor destrin serves as a negative feedback inhibitor of smooth muscle cell differentiation.American journal of physiology. Heart and circulatory physiology · 2021Article
- A homozygous stop-gain variant in ARHGAP42 is associated with childhood interstitial lung disease, systemic hypertension, and immunological findings.PLoS genetics · 2021Article
- CRISPR/Cas9 Mediated Deletion of the Angiotensinogen Gene Reduces Hypertension: A Potential for Cure?Hypertension (Dallas, Tex. : 1979) · 2021Article
- Genetic Variants in Transcription Factor Binding Sites in Humans: Triggered by Natural Selection and Triggers of Diseases.International journal of molecular sciences · 2021Review
- Transforming growth factor β-mediated micromechanics modulates disease progression in primary myelofibrosis.Journal of cellular and molecular medicine · 2020Article
- GRAF3 serves as a blood volume-sensitive rheostat to control smooth muscle contractility and blood pressure.Small GTPases · 2020Article
- Molecular Regulation of the RhoGAP GRAF3 and Its Capacity to Limit Blood Pressure In Vivo.Cells · 2020Article
- Comparative and Functional Genomic Resource for Mechanistic Studies of Human Blood Pressure-Associated Single Nucleotide Polymorphisms.Hypertension (Dallas, Tex. : 1979) · 2020Article
Corrections and comments
- Commented on by
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
We recently demonstrated that selective expression of the Rho GTPase-activating protein ARHGAP42 in smooth muscle cells (SMCs) controls blood pressure by inhibiting RhoA-dependent contractility, providing a mechanism for the blood pressure-associated locus within the ARHGAP42 gene. The goals of the current study were to identify polymorphisms that affect ARHGAP42 expression and to better assess ARHGAP42's role in the development of hypertension. Using DNase I hypersensitivity methods and ENCODE data, we have identified a regulatory element encompassing the ARHGAP42 SNP rs604723 that exhibits strong SMC-selective, allele-specific activity. Importantly, CRISPR/Cas9-mediated deletion of this element in cultured human SMCs markedly reduced endogenous ARHGAP42 expression. DNA binding and transcription assays demonstrated that the minor T allele variation at rs604723 increased the activity of this fragment by promoting serum response transcription factor binding to a cryptic cis-element. ARHGAP42 expression was increased by cell stretch and sphingosine 1-phosphate in a RhoA-dependent manner, and deletion of ARHGAP42 enhanced the progression of hypertension in mice treated with DOCA-salt. Our analysis of a well-characterized cohort of untreated borderline hypertensive patients suggested that ARHGAP42 genotype has important implications in regard to hypertension risk. Taken together, our data add insight into the genetic mechanisms that control blood pressure and provide a potential target for individualized antihypertensive therapies.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.