Sookoian S, Pirola CJ. Liver enzymes, metabolomics and genome-wide association studies: From systems biology to the personalized medicine. World J Gastroenterol 2015; 21(3): 711-725 [PMID: 25624707 DOI: 10.3748/wjg.v21.i3.711]
Corresponding Author of This Article
Silvia Sookoian, MD, PhD, 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, Combatiente de Malvinas 3150, Buenos Aires 1427, Argentina. sookoian.silvia@lanari.fmed.uba.ar
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Editorial
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Jan 21, 2015; 21(3): 711-725 Published online Jan 21, 2015. doi: 10.3748/wjg.v21.i3.711
Liver enzymes, metabolomics and genome-wide association studies: From systems biology to the personalized medicine
Silvia Sookoian, Carlos J Pirola
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
Carlos J Pirola, Department of Molecular Genetics and Biology of Complex Diseases, 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
Author contributions: Pirola CJ and Sookoian S contributed to study concept and design; acquisition of data; analysis and interpretation of data; statistical analysis; drafting of the manuscript; obtained funding and study supervision.
Supported by (in part) Grants PICT 2010-0441 and PICT 2012-0159 (Agencia Nacional de Promoción Científica y Tecnológica) and UBACYT CM04 (Universidad de Buenos Aires).
Conflict-of-interest: The authors have no conflict of interest to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Silvia Sookoian, MD, PhD, 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, Combatiente de Malvinas 3150, Buenos Aires 1427, Argentina. sookoian.silvia@lanari.fmed.uba.ar
Telephone: +54-11-45148701 Fax: +54-11-45238947
Received: September 4, 2014 Peer-review started: September 4, 2014 First decision: October 14, 2014 Revised: October 18, 2014 Accepted: December 14, 2014 Article in press: December 16, 2014 Published online: January 21, 2015 Processing time: 138 Days and 17.3 Hours
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.
Core tip: Genomic, transcriptomic, proteomic, and metabolomic information has changed the classical conception of the meaning that serum concentrations of alanine- and aspartate aminotransferase are merely indicators of hepatocyte membrane disruption. It has given way to a more complex and interconnected view of the importance of liver transaminases in the regulation of systemic metabolic function.
