Liver enzymes, metabolomics and genome-wide association studies: From systems biology to the personalized medicine.

SILVIA SOOKOIAN; CARLOS J. PIROLA

WORLD JOURNAL OF GASTROENTEROLOGY

W J G PRESS

Lugar: Beijing; Año: 2015 vol. 21 p. 711 - 725

1007-9327

For several decades, serum levels of alanine (ALT)and aspartate (AST) aminotransferases have beenregarded as markers of liver injury, including a widerange of etiologies from viral hepatitis to fatty liver.The increasing worldwide prevalence of metabolicsyndrome and cardiovascular disease revealed thattransaminases are strong predictors of type 2 diabetes,coronary heart disease, atherothrombotic risk profile,and overall risk of metabolic disease. Therefore, itis plausible to suggest that aminotransferases aresurrogate biomarkers of ?liver metabolic functioning?beyond the classical concept of liver cellular damage,as their enzymatic activity might actually reflectkey aspects of the physiology and pathophysiologyof the liver function. In this study, we summarizethe background information and recent findings onthe biological role of ALT and AST, and review theknowledge gained from the application of genome-wideapproaches and ?omics? technologies that uncoverednew concepts on the role of aminotransferases inhuman diseases and systemic regulation of metabolicfunctions. Prediction of biomolecular interactionsbetween the candidate genes recently discoveredto be associated with plasma concentrations of liverenzymes showed interesting interconnectivity nodes,which suggest that regulation of aminotransferaseactivity is a complex and highly regulated trait. Finally,links between aminotransferase genes and metabolitesare explored to understand the genetic contributionsto the metabolic diversity.