• The Genetic and Environmental Regulation of Transaminase Activity: Implications for Personalized Medicine
  • Javad Yaghmoorian Khojini,1 Babak Negahdari,2 Ali Eatemadi,3,*
    1. Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
    2. Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
    3. Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran


  • Introduction: Transaminases, specifically alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are enzymes commonly used as biomarkers for liver injury. However, recent research indicates their roles extend beyond simple indicators of liver damage, implicating them in broader metabolic and cardiovascular diseases. Elevated transaminase levels have been linked to conditions such as type 2 diabetes, coronary heart disease, and metabolic syndrome, suggesting that these enzymes reflect complex physiological processes. This review aims to explore the genetic and environmental factors regulating transaminase activity and discuss their implications for personalized medicine.
  • Methods: This review synthesizes data from genome-wide association studies (GWAS), omics technologies, and recent clinical studies to examine the genetic and environmental factors influencing transaminase activity. GWAS has identified several candidate genes associated with transaminase levels, providing insights into the genetic regulation of these enzymes. Additionally, we reviewed studies examining the influence of environmental factors, such as diet and lifestyle, on transaminase activity. The integration of these findings allows for a comprehensive understanding of the regulatory mechanisms governing transaminase levels and their potential as personalized medicine tools.
  • Results: The regulation of transaminase activity is influenced by a complex interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified several key genes associated with ALT and AST levels, including PNPLA3, TM6SF2, and GCKR The PNPLA3 gene, which plays a significant role in lipid metabolism, has been strongly linked to elevated transaminase levels, particularly in the context of non-alcoholic fatty liver disease (NAFLD). Variants in TM6SF2 and GCKR are also implicated in transaminase regulation, further connecting these enzymes to broader metabolic processes. Epigenetic factors, such as DNA methylation, also contribute to the regulation of transaminase levels. For instance, hypermethylation of specific gene promoters can downregulate the expression of enzymes critical for transaminase activity, leading to altered levels and increased disease susceptibility. These findings suggest that genetic predispositions are modulated by epigenetic changes, which can either exacerbate or mitigate the impact of these predispositions. Environmental factors, particularly diet and lifestyle, significantly influence transaminase activity. High-fructose and high-fat diets have been shown to elevate ALT and AST levels, especially in individuals with genetic susceptibility. Conversely, diets rich in fiber and polyunsaturated fats are associated with lower transaminase levels, offering a protective effect. Alcohol consumption is another critical factor, with chronic intake linked to elevated AST levels. The AST/ALT ratio is often used as a marker for alcohol-related liver damage, and genetic variants in alcohol-metabolizing genes can further influence these levels. Physical activity is a beneficial modulator of transaminase levels. Regular exercise is associated with lower ALT and AST levels, likely due to improved metabolic health. This effect is particularly beneficial for individuals with genetic predispositions to elevated transaminase levels, emphasizing the role of lifestyle interventions in managing transaminase activity. In conclusion, the regulation of transaminase activity is governed by a dynamic interaction between genetic, epigenetic, and environmental factors, highlighting the importance of personalized approaches in managing metabolic and liver-related diseases.
  • Conclusion: The regulation of transaminase activity is a multifaceted process involving both genetic and environmental factors. Understanding these regulatory mechanisms is crucial for developing personalized medical approaches that can effectively address the underlying causes of altered transaminase levels. Personalized medicine, which takes into account an individual’s genetic makeup and environmental exposures, offers the potential to tailor interventions that can prevent or mitigate the adverse health outcomes associated with elevated transaminase levels. Future research should focus on further elucidating the genetic pathways involved in transaminase regulation and exploring how these insights can be translated into clinical practice to improve patient outcomes.
  • Keywords: Transaminases, Genetic regulation, Environmental factors, ALT/AST, Personalized medicine