ArticleBritish journal of clinical pharmacology2014
A common hypofunctional genetic variant of GPER is associated with increased blood pressure in women.
Article in British journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- The Association of G Protein-Coupled Estrogen Receptor (GPER) Polymorphisms with Ionizing Radiation Exposure in Healthcare Workers.Journal of clinical medicine · 2026Article
- G-protein coupled estrogen receptor 1 contributes to suppression of angiotensin II hypertension via modulation of AMPA GluA1 in the hypothalamic paraventricular nucleus in a mouse model of post-menopause.Biology of sex differences · 2026Article
- Novel Advances in Our Understanding of Sex-Dependent Control of Blood Pressure.Annual review of physiology · 2026Review
- Renal G protein-coupled estrogen receptor 1 regulates the epithelial sodium channel promoting natriuresis to a greater extent in females.American journal of physiology. Renal physiology · 2025Article
- G-Protein-Coupled Estrogen Receptor 1 and Pregnancy Confer Protection Against Hypertension in Older Females.Circulation · 2025Article
- LNS8801: An Enantiomerically Pure Agonist of the G Protein-Coupled Estrogen Receptor Suitable for Clinical Development.Cancer research communications · 2025Article
- Article
- Endothelin receptor B is required for the blood pressure-lowering effect of G protein-coupled estrogen receptor 1 in ovariectomized rats.American journal of physiology. Renal physiology · 2024Article
- GPER1 signaling restricts macrophage proliferation and accumulation in human hepatocellular carcinoma.Frontiers in immunology · 2024Article
- The Role of G Protein-Coupled Estrogen Receptor (GPER) in Vascular Pathology and Physiology.Biomolecules · 2023Review
- Estrogen-mediated mechanisms in hypertension and other cardiovascular diseases.Journal of human hypertension · 2023Review
- The G protein-coupled oestrogen receptor GPER in health and disease: an update.Nature reviews. Endocrinology · 2023Review
- G protein-coupled estrogen receptor: a promising therapeutic target for aldosterone-induced hypertension.Frontiers in endocrinology · 2023Review
- G-Protein-Coupled Estrogen Receptor Expression in Rat Uterine Artery Is Increased by Pregnancy and Induces Dilation in a CaInternational journal of molecular sciences · 2022Article
- Emerging Roles for G Protein-Coupled Estrogen Receptor 1 in Cardio-Renal Health: Implications for Aging.Biomolecules · 2022Review
- Deciphering pathogenicity of variants of uncertain significance with CRISPR-edited iPSCs.Trends in genetics : TIG · 2021Review
- Activation of G protein-coupled estrogen receptor 1 ameliorates proximal tubular injury and proteinuria in Dahl salt-sensitive female rats.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Signalling mechanisms in the cardiovascular protective effects of estrogen: With a focus on rapid/membrane signalling.Current research in physiology · 2021Review
- Bazi Bushen Capsule Alleviates Post-Menopausal Atherosclerosis via GPER1-Dependent Anti-Inflammatory and Anti-Apoptotic Effects.Frontiers in pharmacology · 2021Article
- A hypertension patient-derived iPSC model demonstrates a role for G protein-coupled estrogen receptor in hypertension risk and development.American journal of physiology. Cell physiology · 2020Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
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Abstract
aimsActivation of vascular GPER has been linked to vasodepressor effects in animals. However, the significance of GPER regulation on chronic blood pressure control in humans is unknown.
methodsTo examine this question we determined the functional significance of expression of a common missense single nucleotide variant of GPER, P16L in vascular smooth muscle cells, and its association with blood pressure in humans. Further, to validate the importance of carrying GPER P16L in the development of hypertension we assessed allele frequency in a cohort of hard-to-treat hypertensive patients referred to a tertiary care clinic.
resultsExpression of the GPER P16L variant (V) vs. wild type (WT) in rat aortic vascular smooth muscle cells, was associated with a significant decrease in G1 (1 μm, a GPER agonist)-mediated ERK phosphorylation (slope of the function of G1-stimulated ERK phosphorylation: GPER content WT: 16.2, 95% CI 9.9, 22.6; V: 5.0, 95% CI 1.0, 9.0; P < 0.005) and apoptosis (slope of the function of G1-stimulated apoptosis: GPER content: WT: 4.4, 95% CI: 3.4, 5.4; V: 2.5, 95% CI 1.6, 2.3 P < 0.005). Normotensive female subjects, but not male subjects, carrying this hypofunctional variant (allele frequency 22%) have increased blood pressure [mean arterial pressure: P16/P16: 80 ± 1 mmHg (n = 204) vs. P16L carriers: 82 ± 1 mmHg (n = 127), 95% CI for difference: 0.6, 4.0 mmHg, P < 0.05], [systolic blood pressure: P16/P16: 105 ± 1 mmHg vs. P16L carriers: 108 ± 1 mmHg, 95% CI for difference:1.0, 5.1 mmHg, P < 0.05], [diastolic blood pressure: P16/P16: 66 ± 0.5 mmHg vs. P16L carriers 68 ± 0.7, 95% CI for difference: 0.2, 3.6 mmHg, P < 0.05]. Further, the P16L allele frequency was almost two-fold higher in female vs. male hypertensive patients (31% vs. 16%, allele ratio 0.5, 95% CI 0.32, 0.76, P < 0.05).
conclusionsThe common genetic variant, GPER P16L, is hypofunctional and female carriers of this allele have increased blood pressure. There was an increased prevalence in a population of hard-to-treat hypertensive female patients. Cumulatively, these data suggest that in females, impaired GPER function might be associated with increased blood pressure and risk of hypertension.
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