The genetic epidemiology of nonalcoholic fatty liver disease: toward a personalized medicine.

The understanding of the genetic bases of complex diseases such as nonalcoholic fatty liver disease opens new opportunities and challenges. This article explores new tools designed toward moving genomic data into clinical medicine, providing putative answers to more practical questions.

[1]  Luigi Ferrucci,et al.  Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes. , 2008, American journal of human genetics.

[2]  S. Baulande,et al.  Adiponutrin : a transmembrane protein corresponding to a novel dietary-and obesity-linked mRNA specifically expressed in the adipose lineage , 2001 .

[3]  A. Lonardo,et al.  Genetic polymorphisms in non-alcoholic fatty liver disease: interleukin-6-174G/C polymorphism is associated with non-alcoholic steatohepatitis. , 2009, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[4]  S. Sookoian,et al.  Influence of hepatocyte nuclear factor 4alpha (HNF4alpha) gene variants on the risk of type 2 diabetes: a meta-analysis in 49,577 individuals. , 2010, Molecular genetics and metabolism.

[5]  S. Sookoian,et al.  Meta‐analysis of the influence of I148M variant of patatin‐like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease , 2011, Hepatology.

[6]  G. Szabo,et al.  Hypoxia and hypoxia inducible factors: Diverse roles in liver diseases , 2012, Hepatology.

[7]  L. Ferrell,et al.  Ethnicity and nonalcoholic fatty liver disease , 2012, Hepatology.

[8]  Marc Prentki,et al.  Glycerolipid metabolism and signaling in health and disease. , 2008, Endocrine reviews.

[9]  C. Rosenfeld,et al.  Metabolic imprinting by prenatal, perinatal, and postnatal overnutrition: a review. , 2011, Seminars in reproductive medicine.

[10]  N. Lago,et al.  High fat diet-induced liver steatosis promotes an increase in liver mitochondrial biogenesis in response to hypoxia , 2010, Journal of cellular and molecular medicine.

[11]  Gustavo Castaño,et al.  A diagnostic model to differentiate simple steatosis from nonalcoholic steatohepatitis based on the likelihood ratio form of Bayes theorem. , 2009, Clinical biochemistry.

[12]  F. Knop Bile-induced secretion of glucagon-like peptide-1: pathophysiological implications in type 2 diabetes? , 2010, American journal of physiology. Endocrinology and metabolism.

[13]  H. Hausenblas,et al.  Resveratrol and health--a comprehensive review of human clinical trials. , 2011, Molecular nutrition & food research.

[14]  A. Feldstein,et al.  Non‐invasive diagnosis of nonalcoholic fatty liver and nonalcoholic steatohepatitis , 2011, Journal of digestive diseases.

[15]  S. Sookoian,et al.  Genetic variants in STAT3 are associated with nonalcoholic fatty liver disease. , 2008, Cytokine.

[16]  S. Sookoian,et al.  Mitochondrial DNA Depletion in Small‐ and Large‐for‐Gestational‐Age Newborns , 2006, Obesity.

[17]  B. Neuschwander‐Tetri,et al.  Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. , 2010, The New England journal of medicine.

[18]  Guenter Haemmerle,et al.  Lipolysis: pathway under construction , 2005, Current opinion in lipidology.

[19]  B. Staels,et al.  Role of bile acids and bile acid receptors in metabolic regulation. , 2009, Physiological reviews.

[20]  S. Sookoian,et al.  A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity , 2009, Journal of Lipid Research.

[21]  Jonathan C. Cohen,et al.  Expression and Characterization of a PNPLA3 Protein Isoform (I148M) Associated with Nonalcoholic Fatty Liver Disease* , 2011, The Journal of Biological Chemistry.

[22]  C. Byrne Hypoxia and non-alcoholic fatty liver disease. , 2009, Clinical science.

[23]  Bassem A. Hassan,et al.  Gene prioritization through genomic data fusion , 2006, Nature Biotechnology.

[24]  S. Sookoian,et al.  Epigenetic regulation of insulin resistance in nonalcoholic fatty liver disease: Impact of liver methylation of the peroxisome proliferator–activated receptor γ coactivator 1α promoter , 2010, Hepatology.

[25]  Michelle M Wiest,et al.  The plasma lipidomic signature of nonalcoholic steatohepatitis , 2009, Hepatology.

[26]  M. Kumari,et al.  Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome[S] , 2011, Journal of Lipid Research.

[27]  S. Sookoian,et al.  Losartan reduces liver expression of plasminogen activator inhibitor-1 (PAI-1) in a high fat-induced rat nonalcoholic fatty liver disease model. , 2009, Atherosclerosis.

[28]  Nick V. Grishin,et al.  A Sequence Variation (I148M) in PNPLA3 Associated with Nonalcoholic Fatty Liver Disease Disrupts Triglyceride Hydrolysis , 2009, The Journal of Biological Chemistry.

[29]  Gary D. Bader,et al.  The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function , 2010, Nucleic Acids Res..

[30]  S. Sookoian,et al.  The nuclear receptor PXR gene variants are associated with liver injury in nonalcoholic fatty liver disease , 2010, Pharmacogenetics and genomics.

[31]  É. Hajduch,et al.  Protein kinase C isoforms: Mediators of reactive lipid metabolites in the development of insulin resistance , 2011, FEBS letters.

[32]  L. Siculella,et al.  Quercetin inhibits fatty acid and triacylglycerol synthesis in rat‐liver cells , 2009, European journal of clinical investigation.

[33]  A. Feldstein,et al.  Hepatic Lipid Partitioning and Liver Damage in Nonalcoholic Fatty Liver Disease , 2009, Journal of Biological Chemistry.

[34]  T. Saibara,et al.  Polymorphisms of microsomal triglyceride transfer protein gene and manganese superoxide dismutase gene in non-alcoholic steatohepatitis. , 2004, Journal of hepatology.

[35]  F. Anania,et al.  Exendin‐4, a glucagon‐like protein‐1 (GLP‐1) receptor agonist, reverses hepatic steatosis in ob/ob mice , 2006, Hepatology.

[36]  N. Lundbom,et al.  Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors. , 2009, Gastroenterology.

[37]  G Steiner,et al.  Origin of triacylglycerol moiety of plasma very low density lipoproteins in the rat: structural studies. , 1995, Journal of lipid research.

[38]  R. Hernaez,et al.  Genetic factors associated with the presence and progression of nonalcoholic fatty liver disease: a narrative review. , 2012, Gastroenterologia y hepatologia.

[39]  J. Shendure,et al.  Exome sequencing as a tool for Mendelian disease gene discovery , 2011, Nature Reviews Genetics.

[40]  K Szentmihályi,et al.  The effect of citrus flavonoids on the redox state of alimentary-induced fatty liver in rats , 2007, Natural product research.

[41]  S. Souza,et al.  Estrogen Regulation of Adiposity and Fuel Partitioning , 2005, Journal of Biological Chemistry.

[42]  S. Sookoian,et al.  Maternal Pregestational BMI Is Associated With Methylation of the PPARGC1A Promoter in Newborns , 2009, Obesity.

[43]  S. Sookoian,et al.  Cyclooxygenase inhibition Up‐regulates liver carnitine palmitoyltransferase 1A expression and improves fatty liver , 2011, Hepatology.

[44]  Alexander Pertsemlidis,et al.  Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease , 2008, Nature Genetics.

[45]  S. Sookoian,et al.  Gene prioritization based on biological plausibility over genome wide association studies renders new loci associated with type 2 diabetes , 2009, Genetics in Medicine.

[46]  S. Sookoian,et al.  Liver transcriptional profile of atherosclerosis-related genes in human nonalcoholic fatty liver disease. , 2011, Atherosclerosis.