Liver enzymes, metabolomics and genome-wide association studies: from systems biology to the personalized medicine.
For several decades, serum levels of alanine (ALT) and aspartate (AST) aminotransferases have been regarded as markers of liver injury, including a wide range of etiologies from viral hepatitis to fatty liver. The increasing worldwide prevalence of metabolic syndrome and cardiovascular disease revealed that transaminases are strong predictors of type 2 diabetes, coronary heart disease, atherothrombotic risk profile, and overall risk of metabolic disease. Therefore, it is plausible to suggest that aminotransferases are surrogate biomarkers of "liver metabolic functioning" beyond the classical concept of liver cellular damage, as their enzymatic activity might actually reflect key aspects of the physiology and pathophysiology of the liver function. In this study, we summarize the background information and recent findings on the biological role of ALT and AST, and review the knowledge gained from the application of genome-wide approaches and "omics" technologies that uncovered new concepts on the role of aminotransferases in human diseases and systemic regulation of metabolic functions. Prediction of biomolecular interactions between the candidate genes recently discovered to be associated with plasma concentrations of liver enzymes showed interesting interconnectivity nodes, which suggest that regulation of aminotransferase activity is a complex and highly regulated trait. Finally, links between aminotransferase genes and metabolites are explored to understand the genetic contributions to the metabolic diversity.
['Sookoian|Silvia|S|', 'Pirola|Carlos J|CJ|']
D000410:Alanine Transaminase D000818:Animals D001219:Aspartate Aminotransferases D015415:Biomarkers D004796:Clinical Enzyme Tests D053263:Gene Regulatory Networks D020022:Genetic Predisposition to Disease D055106:Genome-Wide Association Study D023281:Genomics D040941:Heredity D006801:Humans D008099:Liver D008107:Liver Diseases D055432:Metabolomics D010641:Phenotype D057285:Precision Medicine D011237:Predictive Value of Tests D011379:Prognosis D060066:Protein Interaction Maps D012307:Risk Factors D049490:Systems Biology
Metabolomics Systems biology Aminotransferases Metabolic syndrome Metabolism Transaminases Genetics Alanine-aminotransferase Aspartate-aminotransferase Gene variants Glutamate-oxalacetate transaminase Glutamate-pyruvate transaminase Glutamic acid Nonalcoholic fatty liver Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis PNPLA3 Single nucleotide polymorphisms