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Renin-independent aldosteronism and metabolic dysfunction-associated steatotic liver disease and cirrhosis: A genetic association study.

Renin-independent aldosteronism and metabolic dysfunction-associated steatotic liver disease and cirrhosis: A genetic association study.

Authors :
Zeng Q
Luo X
Chen X
Luo W
Li R
Yang S
Yang J
Shu X
Li Q
Hu J
Ma L
Mantzoros CS
Source :
Clinical nutrition (Edinburgh, Scotland) [Clin Nutr] 2025 Jan; Vol. 44, pp. 193-200. Date of Electronic Publication: 2024 Dec 16.
Publication Year :
2025

Abstract

Background & Aims: Renin-independent aldosteronism (RIA) refers to a spectrum of autonomous aldosterone hypersecretion. We aimed to explore the genetical relationship between RIA and metabolic dysfunction-associated steatotic liver disease (MASLD) and cirrhosis.<br />Methods: We included 125357 participants from the cohort of United Kingdom Biobank. We calculated a polygenic risk score (PRS) for RIA on the basis of reported data from genome-wide association studies, and performed an analysis of Phenome Wide Association Studies (PheWAS) on diverse outcomes. We explored the genetical relationship between RIA and MASLD or cirrhosis by using Mendelian randomization analysis.<br />Results: An increased RIA PRS was associated with higher risks of MASLD and MASLD related cirrhosis, and the well-defined RIA related target organ damages such as hypertension or kidney diseases was also significant in the PheWAS analysis. When compared to individuals with low RIA PRS (tertile 1, 0.41-9.89), those with high RIA PRS (tertile 3, 13.58-23.16) showed significantly higher odds ratio (OR) of MASLD (OR 1.28, 95 % confidence interval [CI] 1.09-1.49) and cirrhosis (OR 1.49, 95%CI 1.03-2.16). In analyses of two-sample Mendelian randomization, genetically predicted RIA significantly correlated with elevated risks of MASLD and cirrhosis (inverse variance weighted odds ratio [95 % CI]: 1.05 [1.01-1.09]) for MASLD, 1.08 [1.02-1.13] for cirrhosis), meanwhile we observed no significant directional pleiotropy or heterogeneity.<br />Conclusion: Renin-independent aldosteronism is genetically associated with higher risks of MASLD and cirrhosis. Targeted treatment of autonomous aldosterone secretion may alleviate MASLD progression.<br />Competing Interests: Conflict of interest The authors report no conflicts of interest.<br /> (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Details

Language :
English
ISSN :
1532-1983
Volume :
44
Database :
MEDLINE
Journal :
Clinical nutrition (Edinburgh, Scotland)
Publication Type :
Academic Journal
Accession number :
39708461
Full Text :
https://doi.org/10.1016/j.clnu.2024.12.011