• 1
    Prentice AM. The emerging epidemic of obesity in developing countries. Int J Epidemiol 2007;35:93-99.
  • 2
    Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002;346:1221-1231.
  • 3
    Brunt EM, Tiniakos DG. Pathological features of NASH. Front Biosci 2005;10:1475-1484.
  • 4
    Tiniakos DG, Vos MB, Brunt EM. Nonalcoholic fatty liver disease: pathology and pathogenesis. Annu Rev Pathol 2010;5:145-171.
  • 5
    Chitturi S, Wong VW, Farrell G. Nonalcoholic fatty liver disease in Asia: firmly entrenched and rapidly gaining ground. J Gastroenterol Hepatol 2011;26:163-172.
  • 6
    Romeo S, Kozlitina J, Xing C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008;40:1461-1465.
  • 7
    Sookoian S, Pirola CJ. 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. Hepatology 2011;53:1883-1894.
  • 8
    Kotronen A, Johansson LE, Johansson LM, et al. A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans. Diabetologia 2009;52:1056-1060.
  • 9
    Kollerits B, Coassin S, Kiechl S, et al. A common variant in the adiponutrin gene influences liver enzyme values. J Med Genet 2010;47:116-119.
  • 10
    Valenti L, Al-Serri A, Daly AK, et al. Homozygosity for the patatin-like phospholipase-3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease. Hepatology 2010;51:1209-1217.
  • 11
    Rotman Y, Koh C, Zmuda JM, Kleiner DE, Liang TJ; NASH CRN. The association of genetic variability in patatin-like phospholipase domain-containing protein 3 (PNPLA3) with histological severity of nonalcoholic fatty liver disease. Hepatology 2010;52:894-903.
  • 12
    Speliotes EK, Butler JL, Palmer CD, et al. PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease. Hepatology 2010;52:904-912.
  • 13
    Petersen KF, Dufour S, Hariri A, et al. Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease. N Engl J Med 2010;362:1082-1089.
  • 14
    Zannis VI, Cole FS, Jackson CL, Kurnit DM, Karathanasis SK. Distribution of apolipoprotein A-I, C-II, C-III, and E mRNA in fetal human tissues. Time-dependent induction of apolipoprotein E mRNA by cultures of human monocyte-macrophages. Biochemistry 1985;24:4450-4455.
  • 15
    Ito Y, Azrolan N, O'Connell A, Walsh A, Breslow JL. Hypertriglyceridemia as a result of human apo CIII gene expression in transgenic mice. Science 1990;249:790-793.
  • 16
    Caron S, Verrijken A, Mertens I, et al. Transcriptional activation of apolipoprotein CIII expression by glucose may contribute to diabetic dyslipidemia. Arterioscler Thromb Vasc Biol 2011;31:513-519.
  • 17
    Kozlitina J, Boerwinkle E, Cohen JC, Hobbs HH. Dissociation between APOC3 variants, hepatic triglyceride content and insulin resistance. Hepatology 2011;53:467-474.
  • 18
    Sentinelli F, Romeo S, Maglio C, et al. Lack of effect of apolipoprotein C3 polymorphisms on indices of liver steatosis, lipid profile and insulin resistance in obese Southern Europeans. Lip Health Dis 2011;10:93.
  • 19
    Valenti L, Nobili V, Al-Serri A, et al. The APOC3 T-455C and C-482T promoter region polymorphisms are not associated with the severity of liver damage independently of PNPLA3 I148M genotype in patients with nonalcoholic fatty liver. J Hepatol 2011;55:1409-1414.
  • 20
    Hyysalo J, Stojkovic I, Kotronen A, et al. Genetic variation in PNPLA3 but not APOC3 influences liver fat in NAFLD. J Gastroenterol Hepatol 2012;27:951-956.
  • 21
    Santoro N, Zhang CK, Zhao H, et al. Variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver in obese children and adolescents. Hepatology 2012;55:781-789.
  • 22
    Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.
  • 23
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and β-cell function from fasting glucose and insulin concentrations in man. Diabetologia 1985;28:412-419.
  • 24
    van der Kooy K, Seidell JC. Techniques for the measurement of visceral fat: a practical guide. Int J Obes Relat Metab Disord 1993;17:187-196.
  • 25
    Taylor KJ, Sullivan D, Simeone J, Rosenfield AT. Scintigraphy, ultrasound and CT scanning of the liver. Yale J Biol Med 1977;50:437-455.
  • 26
    Merkel C, Bolognesi M, Bellon S, Bianco S, Honisch B, Lampe H. Aminopyrine breath test in the prognostic evaluation of patients with cirrhosis. Gut 1992;33:836-842.
  • 27
    Farrell GC, George J, de la M, Hall P, McCullough AJ, editors. Fatty Liver Disease: NASH and Related Disorders. 1st ed. Massachusetts: Blackwell Publishing; 2005. pp 1-12.
  • 28
    Cosgrove DO, Meire H, Dewbury K, editors. Abdominal and General Ultrasound. 3rd ed. New York: Churchill Livingstone; 1994. pp 227-242.
  • 29
    Saverymuttu SH, Joseph AE, Maxwell JD. Ultrasound scanning in the detection of hepatic fibrosis and steatosis. Br Med J (Clin Res Ed) 1986;292:13-15.
  • 30
    Joy D, Thava VR, Scott BB. Diagnosis of fatty liver disease: is biopsy necessary? Eur J Gastroenterol Hepatol 2003;15:539-543.
  • 31
    Brunt EM, Kleiner DE, Wilson LA, Belt P, Neuschwander-Tetri BA; NASH Clinical Research Network (CRN). Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology 2011;53:810-820.
  • 32
    Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41:1313-1321.
  • 33
    Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1998;16:1215.
  • 34
    Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;162:156-159.
  • 35
    Ott J. Documentation to LINKAGE UTILITY Programs,, accessed on April 20, 2011.
  • 36
    Gauderman WJ, Morrison JM. QUANTO 1.1: a computer program for power and sample size calculations for genetic-epidemiology studies,, accessed on April 20, 2011.
  • 37
    Huang Y, Cohen JC, Hobbs HH. Expression and characterization of a PNPLA3 protein isoform (I148M) associated with nonalcoholic fatty liver disease. J Biol Chem 2011;286:37085-37093.
  • 38
    Sookoian S, Castaño GO, Burgueño AL, Gianotti TF, Rosselli MS, Pirola CJ. A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity. J Lipid Res 2009;50:2111-2116.
  • 39
    Speliotes EK, Yerges-Armstrong LM, Wu J, et al. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genetics 2011;7:e1001324.
  • 40
    Brunt EM. Histopathology of non-alcoholic fatty liver disease. Clin Liver Dis 2009;13:533-544.