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

作　　者：Silvia Sookoian Carlos J Pirola 

机构地区：[1]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 [2]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

出　　处：《World Journal of Gastroenterology》2015年第3期711-725,共15页世界胃肠病学杂志（英文版）

基　　金：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)

摘　　要：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.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.

关 键 词：TRANSAMINASES AMINOTRANSFERASES Alanineaminotransf 

分 类 号：R575[医药卫生—消化系统]