title: Liver enzymes, metabolomics and genome-wide association studies: from systems biology to the personalized medicine.
abstract: 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.
authors.affiliation: Silvia Sookoian, Department of Clinical and Molecular Hepatology, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires - National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires, Buenos Aires 1427, Argentina.
authors.forename: Silvia
authors.initials: S
authors.lastname: Sookoian
authors.affiliation: Silvia Sookoian, Department of Clinical and Molecular Hepatology, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires - National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires, Buenos Aires 1427, Argentina.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Pirola
mesh_terms: D000410:Alanine Transaminase / Q000097:blood* / Q000235:genetics; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood* / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D004796:Clinical Enzyme Tests / Q000379:methods; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods; D040941:Heredity; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008107:Liver Diseases / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D055432:Metabolomics / Q000379:methods; D010641:Phenotype; D057285:Precision Medicine / Q000379:methods; D011237:Predictive Value of Tests; D011379:Prognosis; D060066:Protein Interaction Maps; D012307:Risk Factors; D049490:Systems Biology / Q000379:methods
chemical_list: D015415:Biomarkers; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Alanine-aminotransferase; Aminotransferases; Aspartate-aminotransferase; Gene variants; Genetics; Glutamate-oxalacetate transaminase; Glutamate-pyruvate transaminase; Glutamic acid; Metabolic syndrome; Metabolism; Metabolomics; Nonalcoholic fatty liver; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; PNPLA3; Single nucleotide polymorphisms; Systems biology; Transaminases