ArticleThe Journal of clinical endocrinology and metabolism2022
Salt Sensitivity of Blood Pressure and Aldosterone: Interaction Between the Lysine-specific Demethylase 1 Gene, Sex, and Age.
Article in The Journal of clinical endocrinology and metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Review
- Sex differences in cardiovascular‑kidney‑metabolic syndrome: From pathogenesis to treatment response (Review).International journal of molecular medicine · 2026Review
- Integrated mechanisms linking sodium-potassium imbalance to salt-sensitive hypertension.Physiological reports · 2025Review
- Salt sensitivity of blood pressure: mechanisms and sex-specific differences.Nature reviews. Cardiology · 2025Review
- Increased Salt-Sensitive Blood Pressure in Women vs Men: Is Relative Hyperaldosteronism the Mechanism?The Journal of clinical endocrinology and metabolism · 2025Article
- Salt-sensitive hypertension: role of endothelial and vascular dysfunction and sex.Frontiers in pharmacology · 2025Review
- Striatin Gene Variants Are Associated With Salt Sensitivity of Blood Pressure by Mechanisms That Differ in Women and Men.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Less sodium, more potassium, or both: population-wide strategies to prevent hypertension.American journal of physiology. Renal physiology · 2023Review
- Salt Sensitivity of Blood Pressure in Women.Hypertension (Dallas, Tex. : 1979) · 2023Review
- Importance of Micromilieu for Pathophysiologic Mineralocorticoid Receptor Activity-When the Mineralocorticoid Receptor Resides in the Wrong Neighborhood.International journal of molecular sciences · 2022Review
- Salt Sensitivity of Blood Pressure and Aldosterone: Interaction Between the Lysine-specific Demethylase 1 Gene, Sex, and Age.The Journal of clinical endocrinology and metabolism · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
contextSalt sensitivity of blood pressure (SSBP) is associated with increased cardiovascular risk, especially in individuals of African descent, although the underlying mechanisms remain obscure. Lysine-specific demethylase 1 (LSD1) is a salt-sensitive epigenetic regulator associated with SSBP and aldosterone dysfunction. An LSD1 risk allele in humans is associated with SSBP and lower aldosterone levels in hypertensive individuals of African but not European descent. Heterozygous knockout LSD1 mice display SSBP and aldosterone dysregulation, but this effect is modified by age and biological sex. This might explain differences in cardiovascular risk with aging and biological sex in humans.
objectiveThis work aims to determine if LSD1 risk allele (rs587618) carriers of African descent display a sex-by-age interaction with SSBP and aldosterone regulation.
methodsWe analyzed 297 individuals of African and European descent from the HyperPATH cohort. We performed multiple regression analyses for outcome variables related to SSBP and aldosterone.
resultsLSD1 risk allele carriers of African (but not European) descent had greater SSBP than nonrisk homozygotes. Female LSD1 risk allele carriers of African descent had greater SSBP, mainly relationship-driven by women with low estrogen (postmenopausal). There was a statistically significant LSD1 genotype-sex interaction in aldosterone response to angiotensin II stimulation in individuals aged 50 years or younger, with female carriers displaying decreased aldosterone responsiveness.
conclusionSSBP associated with LSD1 risk allele status is driven by women with a depleted estrogen state. Mechanisms related to a resistance to develop SSBP in females are uncertain but may relate to an estrogen-modulating effect on mineralocorticoid receptor (MR) activation and/or LSD1 epigenetic regulation of the MR.
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Registered trials
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