Trial reportJournal of the American Society of Hypertension : JASH2014
Genetic variation in CYP4A11 and blood pressure response to mineralocorticoid receptor antagonism or ENaC inhibition: an exploratory pilot study in African Americans.
Trial report in Journal of the American Society of Hypertension : JASH, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Patient-Specific Factors Predicting Renal Denervation Response in Patients With Hypertension: A Systematic Review and Meta-Analysis.Journal of the American Heart Association · 2024Pooled it
- Genetic Variants Associated With Uncontrolled Blood Pressure on Thiazide Diuretic/β-Blocker Combination Therapy in the PEAR (Pharmacogenomic Evaluation of Antihypertensive Responses) and INVEST (International Verapamil-SR Trandolapril Study) Trials.Journal of the American Heart Association · 2017Trial
- Joint Analysis of Multiple Omics to Describe the Biological Characteristics of Resistant Hypertension.Journal of clinical hypertension (Greenwich, Conn.) · 2025Article
- Thai pharmacogenomics database -2 (TPGxD-2) sequel to TPGxD-1, analyzing genetic variants in 26 non-VIPGx genes within the Thai population.Clinical and translational science · 2024Article
- Review of adult gender transition medications: mechanisms, efficacy measures, and pharmacogenomic considerations.Frontiers in endocrinology · 2023Review
- The epithelial sodium channel in inflammation and blood pressure modulation.Frontiers in cardiovascular medicine · 2023Review
- Pharmacogenomics of Hypertension in Africa: Paving the Way for a Pharmacogenetic-Based Approach for the Treatment of Hypertension in Africans.International journal of hypertension · 2023Review
- Bioactive lipids in hypertension.Advances in pharmacology (San Diego, Calif.) · 2023Article
- Promise of Physiological Profiling to Prevent Stroke in People of African Ancestry: Prototyping Ghana.Current neurology and neuroscience reports · 2022Review
- Application of omics in hypertension and resistant hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2022Review
- Salt Sensitivity of Blood Pressure in Blacks and Women: A Role of Inflammation, Oxidative Stress, and Epithelial NaAntioxidants & redox signaling · 2021Review
- A genome-wide association study identifies a novel candidate locus at the DLGAP1 gene with susceptibility to resistant hypertension in the Japanese population.Scientific reports · 2021Article
- Immune Mechanisms of Dietary Salt-Induced Hypertension and Kidney Disease: Harry Goldblatt Award for Early Career Investigators 2020.Hypertension (Dallas, Tex. : 1979) · 2021Review
- Association of Serum Aldosterone and Plasma Renin Activity With Ambulatory Blood Pressure in African Americans: The Jackson Heart Study.Circulation · 2021Article
- Hypertension: Do Inflammation and Immunity Hold the Key to Solving this Epidemic?Circulation research · 2021Review
- Hypothesis: Unrecognized actions of ENaC blockade in improving refractory-resistant hypertension and residual cardiovascular risk.International Journal of Cardiology. Hypertension · 2020Article
- ENaC in Salt-Sensitive Hypertension: Kidney and Beyond.Current hypertension reports · 2020Review
- Effect of Genetic and Nongenetic Factors on the Clinical Response to Mineralocorticoid Receptor Antagonist Therapy in Egyptians with Heart Failure.Clinical and translational science · 2020Observational
- Interpreting stimulated plasma renin and aldosterone to select physiologically individualized therapy for resistant hypertension: importance of the class of stimulating drugs.Hypertension research : official journal of the Japanese Society of Hypertension · 2019Article
- Maintenance of long-term blood pressure control and vascular health by low-dose amiloride-based therapy in hyperaldosteronism.Journal of clinical hypertension (Greenwich, Conn.) · 2019Observational
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
An rs3890011 variant of CYP4A11, which is in linkage disequilibrium with the loss-of-function variant rs1126742, is associated with hypertension in humans. In mice, Cyp4a deficiency results in salt-sensitive hypertension through activation of ENaC. We tested the hypothesis that the rs3890011 variant is associated with blood pressure response to drugs acting via the ENaC pathway. African Americans with volume-dependent, resistant hypertension were randomized to treatment with placebo, spironolactone, amiloride, or combination. Blood pressure responses were analyzed by CYP4A11 genotypes. Rs3890011 (GG:GC:CC = 20:35:28) and rs1126742 (TT:TC:CC = 45:31:7) were in linkage disequilibrium (D' = 1, r = 0.561). Expected small number of rs1126742 CC homozygotes precluded analysis of the effect of this genotype on treatment responses. Spironolactone reduced blood pressure in rs3890011 GG and GC individuals, but not in CC homozygotes (P = .002), whereas amiloride reduced blood pressure similarly in all rs3890011 genotypes. The antihypertensive effects of spironolactone and amiloride were comparable in GG and GC participants, but only amiloride reduced pressure in CC homozygotes (-6.3 ± 7.3/-3.2 ± 4.0 vs. +6.8 ± 7.9/+4.8 ± 8.6 mm Hg, P < .01/<.05). The aldosterone response to spironolactone was also blunted in the CC genotype. In individuals homozygous for the CYP4A11 rs3890011 C allele, blood pressure is resistant to mineralocorticoid receptor antagonism, but sensitive to ENaC inhibition, consistent with ENaC activation. Studies in a larger population are needed to replicate these findings.
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.