Aminotransferases as causal factors for metabolic syndrome: A bidirectional Mendelian randomization study

PLoS One. 2024 Apr 25;19(4):e0302209. doi: 10.1371/journal.pone.0302209. eCollection 2024.

Abstract

Background: Circulating aminotransferases (ALT and AST) have been used as biomarkers for liver injury. The causal relationships between aminotransferases and metabolic syndrome remain ambiguous.

Methods: We conducted bidirectional and multivariable Mendelian randomization (MR) analyses between aminotransferases and traits related to metabolic syndrome using genetic variants obtained from genome-wide association studies (GWASs). MR-PRESSO tests were adopted to remove outliers and eliminate pleiotropy. MR steiger tests were conducted to ensure the correct direction of the causal effects.

Results: Both aminotransferases were risk factors for essential hypertension. ALT is a risk factor for type 2 diabetes. The bidirectional causal relationship between ALT and hyperglycemia, serum lipids, and obesity was demonstrated. The effect of fasting glucose on AST was demonstrated, while type 2 diabetes did not affect AST. The effect of HDL-C on ALT and the effect of triglycerides on AST were found in multivariable MR analyses.

Conclusions: Our bidirectional MR analyses suggest that ALT and AST are causally associated with several metabolic syndrome-related traits, especially hypertension and type 2 diabetes. These findings highlight the potential role of aminotransferases as biomarkers and therapeutic targets for metabolic syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase* / blood
  • Aspartate Aminotransferases / blood
  • Biomarkers / blood
  • Diabetes Mellitus, Type 2* / genetics
  • Genome-Wide Association Study*
  • Humans
  • Hypertension / genetics
  • Mendelian Randomization Analysis*
  • Metabolic Syndrome* / genetics
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Transaminases / blood
  • Transaminases / genetics

Substances

  • Alanine Transaminase
  • Aspartate Aminotransferases
  • Biomarkers
  • Transaminases

Grants and funding

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.