Regulatory variant of Klotho (rs9563124) associates with angiotensin II-stimulated aldosterone and salt-sensitive blood pressure
Authors' conclusion
KL variation, represented by rs9563124, was associated with aldosterone phenotypes and salt-sensitive blood pressure. Functional annotation supports a regulatory mechanism linking KL variation to endocrine responsiveness.
Study context
- Population
- HyperPATH participants studied under controlled dietary sodium conditions; 168 Klotho (KL)-region variants evaluatedHyperPATH
- Participants
- 407 participants
- Comparison
- rs9563124 G allele carriage and aldosterone phenotypes and salt-sensitive blood pressure (SSBP)
- Outcome
- Associations of rs9563124 G allele
Methodological detailscontrolled dietary sodium conditions, candidate-gene variant screening, functional annotation (expression quantitative trait locus (eQTL) and regulatory resources)
- Controlled dietary sodium conditions
- Candidate-gene variant screening
- Functional annotation (eQTL and regulatory resources)
Main finding
As reported in the abstract
SSBP (higher with G allele), beta
2.853
P=0.00185
Baseline aldosterone (higher with G allele), beta
0.733
P=0.00156
Angiotensin II (AngII)-stimulated aldosterone (higher with G allele), beta
1.949
P=0.00062
Aldosterone reactivity (delta-aldosterone), beta
1.23
P=0.00611
Further findings
Age- and sex-stratified associations
- Associations with SSBP stronger in women and participants aged ≥50 years
- Associations with aldosterone phenotypes greater in women and participants <50 years
- Subgroup findings were exploratory
Functional annotation
- Tissue-specific KL eQTLs and allele-specific transcription factor motif alterations identified, supporting a regulatory role
Original publication
Regulatory variant of Klotho (rs9563124) associates with angiotensin II-stimulated aldosterone and salt-sensitive blood pressure. J Clin Endocrinol Metab. Published 18 August 2026. doi:10.
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