Genetic Factors That Affect Risk of Alcoholic and Nonalcoholic Fatty Liver Disease

Gastroenterology

Volumn 150, Issue 8, 2016, Pages 1728-1744.e7

  Anstee, Quentin M ^a   Seth, Devanshi ^b,c   Day, Christopher P ^a  

^a NEWCASTLE UNIVERSITY   (United Kingdom)

^b ROYAL PRINCE ALFRED HOSPITAL   (Australia)

^c UNIVERSITY OF SYDNEY   (Australia)

Author keywords

ALD; Cirrhosis; Gene; NAFLD; PNPLA3; TM6SF2

Indexed keywords

ALCOHOL CONSUMPTION; ALCOHOL METABOLISM; ALCOHOLIC FATTY LIVER; ARTICLE; CARBOHYDRATE METABOLISM; CLINICAL FEATURE; DISEASE SEVERITY; DNA MODIFICATION; ETHNIC DIFFERENCE; GENE; GENETIC RISK; GENOME-WIDE ASSOCIATION STUDY; HEREDITY; HUMAN; INSULIN SENSITIVITY; LIPID METABOLISM; LIVER FIBROSIS; NONALCOHOLIC FATTY LIVER; OXIDATIVE STRESS; PATHOGENESIS; PNPLA3 GENE; PRIORITY JOURNAL; RISK FACTOR; TM6SF2 GENE; GENETIC PREDISPOSITION; GENETICS;

FATTY LIVER, ALCOHOLIC; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; NON-ALCOHOLIC FATTY LIVER DISEASE; RISK FACTORS;

EID: 84971290254     PISSN: 00165085     EISSN: 15280012     Source Type: Journal    
DOI: 10.1053/j.gastro.2016.01.037     Document Type: Article

References (254)

1. A.J. Sanyal American Gastroenterological Association. AGA technical review on nonalcoholic fatty liver disease Gastroenterology 123 2002 1705 1725
2. Q.M. Anstee, G. Targher, and C.P. Day Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis Nat Rev Gastroenterol Hepatol 10 2013 330 344
3. C.S. Lieber, D.P. Jones, and L.M. Decarli Effects of prolonged ethanol intake: production of fatty liver despite adequate diets J Clin Invest 44 1965 1009 1021
4. C.S. Lieber, and L.M. Decarli Animal models of ethanol dependence and liver injury in rats and baboons Fed Proc 35 1976 1232 1236
5. E. Brandon-Warner, L.W. Schrum, C.M. Schmidt, and et al. Rodent models of alcoholic liver disease: of mice and men Alcohol 46 2012 715 725
6. S. Bellentani, G. Saccoccio, G. Costa, and et al. Drinking habits as cofactors of risk for alcohol induced liver damage. The Dionysos Study Group Gut 41 1997 845 850
7. U. Becker, A. Deis, T.I. Sorensen, and et al. Prediction of risk of liver disease by alcohol intake, sex, and age: a prospective population study Hepatology 23 1996 1025 1029
8. P. Angulo The natural history of NAFLD G. Farrell, A.J. McCulloch, C. Day, Non-alcoholic fatty liver disease: a practical guide 2013 Wiley Blackwell Press Chichester, United Kingdom 37 45
9. S. Singh, A.M. Allen, Z. Wang, and et al. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies Clin Gastroenterol Hepatol 13 2015 643 654 e9
10. S. McPherson, T. Hardy, E. Henderson, and et al. Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management J Hepatol 62 2015 1148 1155
11. C.P. Day Pathogenesis of steatohepatitis Best Pract Res Clin Gastroenterol 16 2002 663 678
12. Q.M. Anstee, A.K. Daly, and C.P. Day Genetics of alcoholic and nonalcoholic fatty liver disease Semin Liver Dis 31 2011 128 146
13. G. Corrao, V. Bagnardi, A. Zambon, and et al. A meta-analysis of alcohol consumption and the risk of 15 diseases Prev Med 38 2004 613 619
14. M.R. Teli, C.P. Day, A.D. Burt, and et al. Determinants of progression to cirrhosis or fibrosis in pure alcoholic fatty liver Lancet 346 1995 987 990
15. Q.M. Anstee, S. Knapp, E.P. Maguire, and et al. Mutations in the Gabrb1 gene promote alcohol consumption through increased tonic inhibition Nat Commun 4 2013 2816
16. L. Midanik Familial alcoholism and problem drinking in a national drinking practices survey Addict Behav 8 1983 133 141
17. A. Agrawal, and M.T. Lynskey Are there genetic influences on addiction: evidence from family, adoption and twin studies Addiction 103 2008 1069 1081
18. Q.M. Anstee, A.K. Daly, and C.P. Day Genetics of alcoholic liver disease Semin Liver Dis 35 2015 361 374
19. U. Becker, M. Gronbaek, D. Johansen, and et al. Lower risk for alcohol-induced cirrhosis in wine drinkers Hepatology 35 2002 868 875
20. G. Askgaard, M. Gronbaek, M.S. Kjaer, and et al. Alcohol drinking pattern and risk of alcoholic liver cirrhosis: a prospective cohort study J Hepatol 62 2015 1061 1067
21. D. Johansen, K. Friis, E. Skovenborg, and et al. Food buying habits of people who buy wine or beer: cross sectional study BMJ 332 2006 519 522
22. M. Rotily, J.P. Durbec, P. Berthezene, and et al. Diet and alcohol in liver cirrhosis: a case-control study Eur J Clin Nutr 44 1990 595 603
23. S. Naveau, V. Giraud, E. Borotto, and et al. Excess weight risk factor for alcoholic liver disease Hepatology 25 1997 108 111
24. T.-K. Li Quantifying the risk for alcohol-use and alcohol-attributable health disorders: present findings and future research needs J Gastroenterol Hepatol 23 2008 S2 S8
25. B. Raynard, A. Balian, D. Fallik, and et al. Risk factors of fibrosis in alcohol-induced liver disease Hepatology 35 2002 635 638
26. H. Iturriaga, D. Bunout, S. Hirsch, and et al. Overweight as a risk factor or a predictive sign of histological liver damage in alcoholics Am J Clin Nutr 47 1988 235 238
27. B. Liu, A. Balkwill, G. Reeves, and et al. Body mass index and risk of liver cirrhosis in middle aged UK women: prospective study BMJ 340 2010 c912
28. C.L. Hart, D.S. Morrison, G.D. Batty, and et al. Effect of body mass index and alcohol consumption on liver disease: analysis of data from two prospective cohort studies BMJ 340 2010 c1240
29. T. Poynard, P. Bedossa, and P. Opolon Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups Lancet 349 1997 825 832
30. T. Poynard, V. Ratziu, F. Charlotte, and et al. Rates and risk factors of liver fibrosis progression in patients with chronic hepatitis c J Hepatol 34 2001 730 739
31. J. Dixon, P. Bhathal, and P. O'Brian Non-alcoholic fatty liver disease: predictors of non-alcoholic steatohepatitis and liver fibrosis in the severely obese Gastroenterology 121 2001 91 100
32. H.M. Parker, N.A. Johnson, C.A. Burdon, and et al. Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta-analysis J Hepatol 56 2012 944 951
33. A. Abid, O. Taha, W. Nseir, and et al. Soft drink consumption is associated with fatty liver disease independent of metabolic syndrome J Hepatol 51 2009 918 924
34. M.F. Abdelmalek, A. Suzuki, C. Guy, and et al. Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease Hepatology 51 2010 1961 1971
35. S. Saab, D. Mallam, G.A. Cox 2nd, and et al. Impact of coffee on liver diseases: a systematic review Liver Int 34 2014 495 504
36. J.W. Molloy, C.J. Calcagno, C.D. Williams, and et al. Association of coffee and caffeine consumption with fatty liver disease, nonalcoholic steatohepatitis, and degree of hepatic fibrosis Hepatology 55 2012 429 436
37. A.L. Klatsky, C. Morton, N. Udaltsova, and et al. Coffee, cirrhosis, and transaminase enzymes Arch Intern Med 166 2006 1190 1195
38. L. Zhao Genomics: the tale of our other genome Nature 465 2010 879 880
39. E.M. Quigley, and H.P. Monsour The gut microbiota and nonalcoholic fatty liver disease Semin Liver Dis 35 2015 262 269
40. J.N. Hirschhorn, and Z.K. Gajdos Genome-wide association studies: results from the first few years and potential implications for clinical medicine Annu Rev Med 62 2011 11 24
41. I.R. Willner, B. Waters, S.R. Patil, and et al. Ninety patients with nonalcoholic steatohepatitis: insulin resistance, familial tendency, and severity of disease Am J Gastroenterol 96 2001 2957 2961
42. V.M. Struben, E.E. Hespenheide, and S.H. Caldwell Nonalcoholic steatohepatitis and cryptogenic cirrhosis within kindreds Am J Med 108 2000 9 13
43. J.B. Schwimmer, M.A. Celedon, J.E. Lavine, and et al. Heritability of nonalcoholic fatty liver disease Gastroenterology 136 2009 1585 1592
44. J. Makkonen, K.H. Pietilainen, A. Rissanen, and et al. Genetic factors contribute to variation in serum alanine aminotransferase activity independent of obesity and alcohol: a study in monozygotic and dizygotic twins J Hepatol 50 2009 1035 1042
45. R. Loomba, N. Schork, C.H. Chen, and et al. Heritability of hepatic fibrosis and steatosis based on a prospective twin study Gastroenterology 149 2015 1784 1793
46. J.D. Browning, L.S. Szczepaniak, R. Dobbins, and et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity Hepatology 40 2004 1387 1395
47. J.D. Browning, K.S. Kumar, M.H. Saboorian, and et al. Ethnic differences in the prevalence of cryptogenic cirrhosis Am J Gastroenterol 99 2004 292 298
48. R. Guerrero, G.L. Vega, S.M. Grundy, and et al. Ethnic differences in hepatic steatosis: an insulin resistance paradox? Hepatology 49 2009 791 801
49. K. Bambha, P. Belt, M. Abraham, and et al. Ethnicity and nonalcoholic fatty liver disease Hepatology 55 2012 769 780
50. L.S. Szczepaniak, P. Nurenberg, D. Leonard, and et al. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population Am J Physiol Endocrinol Metab 288 2005 E462 E468
51. N. Sato, K.O. Lindros, E. Baraona, and et al. Sex difference in alcohol-related organ injury Alcohol Clin Exp Res 25 2001 40S 45S
52. F.S. Stinson, B.F. Grant, and M.C. Dufour The critical dimension of ethnicity in liver cirrhosis mortality statistics Alcohol Clin Exp Res 25 2001 1181 1187
53. T. Reed, W.F. Page, R.J. Viken, and et al. Genetic predisposition to organ-specific endpoints of alcoholism Alcohol Clin Exp Res 20 1996 1528 1533
54. Z. Hrubec, and G.S. Omenn Evidence of genetic predisposition to alcoholic cirrhosis and psychosis: twin concordances for alcoholism and its biological end points by zygosity among male veterans Alcohol Clin Exp Res 5 1981 207 215
55. J.B. Whitfield, K. Rahman, P.S. Haber, and et al. Brief report: genetics of alcoholic cirrhosis-GenomALC multinational study Alcohol Clin Exp Res 39 2015 836 842
56. A. Said, J. Williams, J. Holden, and et al. The prevalence of alcohol-induced liver disease and hepatitis C and their interaction in a tertiary care setting Clin Gastroenterol Hepatol 2 2004 928 934
57. N.C. Fisher, J. Hanson, A. Phillips, and et al. Mortality from liver disease in the West Midlands, 1993-2000: observational study BMJ 325 2002 312 313
58. S. Romeo, J. Kozlitina, C. Xing, and et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease Nat Genet 40 2008 1461 1465
59. W.Y. Wang, B.J. Barratt, D.G. Clayton, and et al. Genome-wide association studies: theoretical and practical concerns Nat Rev Genet 6 2005 109 118
60. D. Altshuler, M.J. Daly, and E.S. Lander Genetic mapping in human disease Science 322 2008 881 888
61. L.R. Cardon, and J.I. Bell Association study designs for complex diseases Nat Rev Genet 2 2001 91 99
62. J.N. Hirschhorn Genomewide association studies-illuminating biologic pathways N Engl J Med 360 2009 1699 1701
63. T.A. Manolio, L.D. Brooks, and F.S. Collins A HapMap harvest of insights into the genetics of common disease J Clin Invest 118 2008 1590 1605
64. J. Hardy, and A. Singleton Genomewide association studies and human disease N Engl J Med 360 2009 1759 1768
65. J.N. Hirschhorn, and M.J. Daly Genome-wide association studies for common diseases and complex traits Nat Rev Genet 6 2005 95 108
66. T.A. Manolio, F.S. Collins, N.J. Cox, and et al. Finding the missing heritability of complex diseases Nature 461 2009 747 753
67. N. Chalasani, X. Guo, R. Loomba, and et al. Genome-wide association study identifies variants associated with histologic features of nonalcoholic fatty liver disease Gastroenterology 139 2010 1567 1576 1576 e1-6
68. E.K. Speliotes, L.M. Yerges-Armstrong, J. Wu, and et al. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits PLoS Genet 7 2011 e1001324
69. Q.M. Anstee, R. Darlay, J.B. Leathart, and et al. Genome-wide association analysis confirms importance of PNPLA3 and identifies novel variants associated with histologically progressive steatohepatitis in NAFLD Hepatology 56 2012 265A 266A
70. T. Kawaguchi, Y. Sumida, A. Umemura, and et al. Genetic polymorphisms of the human PNPLA3 gene are strongly associated with severity of non-alcoholic fatty liver disease in Japanese PLoS One 7 2012 e38322
71. M.F. Feitosa, M.K. Wojczynski, K.E. North, and et al. The ERLIN1-CHUK-CWF19L1 gene cluster influences liver fat deposition and hepatic inflammation in the NHLBI Family Heart Study Atherosclerosis 228 2013 175 180
72. J. Kozlitina, E. Smagris, S. Stender, and et al. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease Nat Genet 46 2014 352 356
73. J.K. DiStefano, C. Kingsley, G. Craig Wood, and et al. Genome-wide analysis of hepatic lipid content in extreme obesity Acta Diabetol 52 2015 373 382
74. S. Buch, F. Stickel, E. Trepo, and et al. A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis Nat Genet 47 2015 1443 1448
75. L. Valenti, A. Al-Serri, A.K. Daly, and et al. Homozygosity for the patatin-like phospholipase-3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease Hepatology 51 2010 1209 1217
76. A. Kotronen, L.E. Johansson, L.M. Johansson, and et al. A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans Diabetologia 52 2009 1056 1060
77. S. Sookoian, G.O. Castano, A.L. Burgueno, and et al. A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity J Lipid Res 50 2009 2111 2116
78. K. Kantartzis, A. Peter, F. Machicao, and et al. Dissociation between fatty liver and insulin resistance in humans carrying a variant of the patatin-like phospholipase 3 gene Diabetes 58 2009 2616 2623
79. Y. Rotman, C. Koh, J.M. Zmuda, and et al. The association of genetic variability in patatin-like phospholipase domain-containing protein 3 (PNPLA3) with histological severity of nonalcoholic fatty liver disease Hepatology 52 2010 894 903
80. S. Romeo, F. Sentinelli, V.M. Cambuli, and et al. The 148M allele of the PNPLA3 gene is associated with indices of liver damage early in life J Hepatol 53 2010 335 338
81. L. Valenti, A. Alisi, E. Galmozzi, and et al. I148M patatin-like phospholipase domain-containing 3 gene variant and severity of pediatric nonalcoholic fatty liver disease Hepatology 52 2010 1274 1280
82. N. Santoro, R. Kursawe, E. D'Adamo, and et al. A common variant in the patatin-like phospholipase 3 gene (PNPLA3) is associated with fatty liver disease in obese children and adolescents Hepatology 52 2010 1281 1290
83. K. Sevastianova, A. Kotronen, A. Gastaldelli, and et al. Genetic variation in PNPLA3 (adiponutrin) confers sensitivity to weight loss-induced decrease in liver fat in humans Am J Clin Nutr 94 2011 104 111
84. J. Shen, G.L. Wong, H.L. Chan, and et al. PNPLA3 gene polymorphism and response to lifestyle modification in patients with nonalcoholic fatty liver disease J Gastroenterol Hepatol 30 2015 139 146
85. C. Tian, R.P. Stokowski, D. Kershenobich, and et al. Variant in PNPLA3 is associated with alcoholic liver disease Nat Genet 42 2010 21 23
86. D. Seth, A.K. Daly, P.S. Haber, and et al. Patatin-like phospholipase domain containing 3: a case in point linking genetic susceptibility for alcoholic and nonalcoholic liver disease Hepatology 51 2010 1463 1465
87. H. Salameh, E. Raff, A. Erwin, and et al. PNPLA3 gene polymorphism is associated with predisposition to and severity of alcoholic liver disease Am J Gastroenterol 110 2015 846 856
88. M.M. Hassan, A. Kaseb, C.J. Etzel, and et al. Genetic variation in the PNPLA3 gene and hepatocellular carcinoma in USA: risk and prognosis prediction Mol Carcinog 52 Suppl 1 2013 E139 E147
89. M.A. Burza, C. Pirazzi, C. Maglio, and et al. PNPLA3 I148M (rs738409) genetic variant is associated with hepatocellular carcinoma in obese individuals Dig Liver Dis 44 2012 1037 1041
90. E. Guyot, A. Sutton, P. Rufat, and et al. PNPLA3 rs738409, hepatocellular carcinoma occurrence and risk model prediction in patients with cirrhosis J Hepatol 58 2013 312 318
91. H.D. Nischalke, C. Berger, C. Luda, and et al. The PNPLA3 rs738409 148M/M genotype is a risk factor for liver cancer in alcoholic cirrhosis but shows no or weak association in hepatitis C cirrhosis PLoS One 6 2011 e27087
92. E. Trepo, E. Guyot, N. Ganne-Carrie, and et al. PNPLA3 (rs738409 C>G) is a common risk variant associated with hepatocellular carcinoma in alcoholic cirrhosis Hepatology 55 2012 1307 1308
93. E. Trepo, P. Nahon, G. Bontempi, and et al. Association between the PNPLA3 (rs738409 C>G) variant and hepatocellular carcinoma: evidence from a meta-analysis of individual participant data Hepatology 59 2014 2170 2177
94. L. Valenti, M. Rumi, E. Galmozzi, and et al. Patatin-like phospholipase domain-containing 3 I148M polymorphism, steatosis, and liver damage in chronic hepatitis C Hepatology 53 2011 791 799
95. E. Falleti, C. Fabris, S. Cmet, and et al. PNPLA3 rs738409C/G polymorphism in cirrhosis: relationship with the aetiology of liver disease and hepatocellular carcinoma occurrence Liver Int 31 2011 1137 1143
96. A.G. Singal, H. Manjunath, A.C. Yopp, and et al. The effect of PNPLA3 on fibrosis progression and development of hepatocellular carcinoma: a meta-analysis Am J Gastroenterol 109 2014 325 334
97. Y.L. Liu, G.L. Patman, J.B. Leathart, and et al. Carriage of the PNPLA3 rs738409 C>G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma J Hepatol 61 2014 75 81
98. Q.M. Anstee, Y.L. Liu, C.P. Day, and et al. Reply to: HCC and liver disease risk in homozygous PNPLA3 p.I148M carriers approach monogenic inheritance J Hepatol 62 2015 982 983
99. Q.M. Anstee, and C.P. Day The genetics of nonalcoholic fatty liver disease: spotlight on PNPLA3 and TM6SF2 Semin Liver Dis 35 2015 270 290
100. A. Gorden, R. Yang, L.M. Yerges-Armstrong, and et al. Genetic variation at NCAN locus is associated with inflammation and fibrosis in non-alcoholic fatty liver disease in morbid obesity Hum Hered 75 2013 34 43
101. Q.M. Anstee, and C.P. Day The genetics of NAFLD Nat Rev Gastroenterol Hepatol 10 2013 645 655
102. Y.L. Liu, H.L. Reeves, A.D. Burt, and et al. TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease Nat Commun 5 2014 4309
103. P. Dongiovanni, S. Petta, C. Maglio, and et al. Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease Hepatology 61 2015 506 514
104. X. Wang, Z. Liu, Z. Peng, and et al. The TM6SF2 rs58542926 T allele is significantly associated with non-alcoholic fatty liver disease in Chinese J Hepatol 62 2015 1438 1439
105. V.W. Wong, G.L. Wong, C.H. Tse, and et al. Prevalence of the TM6SF2 variant and non-alcoholic fatty liver disease in Chinese J Hepatol 61 2014 708 709
106. S. Sookoian, G.O. Castano, R. Scian, and et al. Genetic variation in transmembrane 6 superfamily member 2 and the risk of nonalcoholic fatty liver disease and histological disease severity Hepatology 61 2015 515 525
107. N.D. Palmer, S.K. Musani, L.M. Yerges-Armstrong, and et al. Characterization of European ancestry nonalcoholic fatty liver disease-associated variants in individuals of African and Hispanic descent Hepatology 58 2013 966 975
108. B. Kahali, Y.L. Liu, A.K. Daly, and et al. TM6SF2: catch-22 in the fight against nonalcoholic fatty liver disease and cardiovascular disease? Gastroenterology 148 2015 679 684
109. H. Mahdessian, A. Taxiarchis, S. Popov, and et al. TM6SF2 is a regulator of liver fat metabolism influencing triglyceride secretion and hepatic lipid droplet content Proc Natl Acad Sci U S A 111 2014 8913 8918
110. M. Way, S. Atkinson, A. McQuillin, and et al. A functional variant in tm6sf2 associates with alcohol related cirrhosis risk in a British and Irish population J Hepatol 62 Suppl 2 2015 S772
111. H.D. Nischalke, P. Lutz, B. Kramer, and et al. A common polymorphism in the NCAN gene is associated with hepatocellular carcinoma in alcoholic liver disease J Hepatol 61 2014 1073 1079
112. E. Falleti, A. Cussigh, S. Cmet, and et al. PNPLA3 rs738409 and TM6SF2 rs58542926 variants increase the risk of hepatocellular carcinoma in alcoholic cirrhosis Dig Liver Dis 48 2016 69 75
113. S. Zakhari, and T.-K. Li Determinants of alcohol use and abuse: impact of quantity and frequency patterns on liver disease Hepatology 46 2007 2032 2039
114. P. Couzigou, C. Coutelle, and B. Fleury Alcohol and aldehyde dehydrogenase genotypes, alcoholism and alcohol related disease Alcohol Alcoholism 2 1994 21 27
115. E. Borras, C. Coutelle, A. Rosell, and et al. Genetic polymorphism of alcohol dehydrogenase in Europeans: the ADH2∗2 allele decreases the risk for alcoholism and is associated with ADH3∗1 Hepatology 31 2000 984 989
116. Y.C. Chao, S.R. Liou, Y.Y. Chung, and et al. Polymorphism of alcohol and aldehyde dehydrogenase genes and alcoholic cirrhosis in Chinese patients Hepatology 19 1994 360 366
117. J. Watanabe, S. Hayashi, and K. Kawajiri Different regulation and expression of the human CYP2E1 gene due to the RsaI polymorphism in the 50-flanking region J Biochem 116 1994 321 326
118. S. Hayashi, J. Watanabe, and K. Kawajiri Genetic polymorphisms in the 50 flanking region change transcriptional regulation of the human cytochrome P450 IIE1 gene J Biochem 110 1991 559 565
119. M.W. Yu, A. Gladek-Yarborough, and S. Chiamprasert Cytochrome P450 2E1 and glutathione S-transferase M1 polymorphisms and susceptibility to hepatocellular carcinoma Gastroenterology 109 1995 1266 1273
120. N. Homann, F. Stickel, I.R. Konig, and et al. Alcohol dehydrogenase 1C∗1 allele is a genetic marker for alcohol-associated cancer in heavy drinkers Int J Cancer 118 2006 1998 2002
121. F. Stickel, and C.H. Osterreicher The role of genetic polymorphisms in alcoholic liver disease Alcohol Alcoholism 41 2006 209 224
122. N. Grarup, S.A. Urhammer, J. Ek, and et al. Studies of the relationship between the ENPP1 K121Q polymorphism and type 2 diabetes, insulin resistance and obesity in 7,333 Danish white subjects Diabetologia 49 2006 2097 2104
123. A.J. McGettrick, E.P. Feener, and C.R. Kahn Human insulin receptor substrate-1 (IRS-1) polymorphism G972R causes IRS-1 to associate with the insulin receptor and inhibit receptor autophosphorylation J Biol Chem 280 2005 6441 6446
124. P. Dongiovanni, L. Valenti, R. Rametta, and et al. Genetic variants regulating insulin receptor signalling are associated with the severity of liver damage in patients with non-alcoholic fatty liver disease Gut 59 2010 267 273
125. L. Carulli, I. Canedi, S. Rondinella, and et al. Genetic polymorphisms in non-alcoholic fatty liver disease: interleukin-6-174G/C polymorphism is associated with non-alcoholic steatohepatitis Dig Liver Dis 41 2009 823 828
126. N.L. Beer, N.D. Tribble, L.J. McCulloch, and et al. The P446L variant in GCKR associated with fasting plasma glucose and triglyceride levels exerts its effect through increased glucokinase activity in liver Hum Mol Genet 18 2009 4081 4088
127. N. Santoro, C.K. Zhang, H. Zhao, and et al. Variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver in obese children and adolescents Hepatology 55 2011 781 789
128. L. Valenti, A. Alisi, and V. Nobili Unraveling the genetics of fatty liver in obese children: additive effect of P446L GCKR and I148M PNPLA3 polymorphisms Hepatology 55 2012 661 663
129. Q.M. Anstee, R. Darlay, J. Leathart, and et al. A candidate-gene approach to validation of genetic modifier associations using a large cohort with histologically characterised non-alcoholic fatty liver disease J Hepatol 58 2013 S46
130. S. Petta, L. Miele, E. Bugianesi, and et al. Glucokinase regulatory protein gene polymorphism affects liver fibrosis in non-alcoholic fatty liver disease PLoS One 9 2014 e87523
131. M. Vazquez-Chantada, A. Gonzalez-Lahera, I. Martinez-Arranz, and et al. Solute carrier family 2 member 1 is involved in the development of nonalcoholic fatty liver disease Hepatology 57 2013 505 514
132. A. Tonjes, M. Scholz, M. Loeffler, and et al. Association of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma with pre-diabetic phenotypes: meta-analysis of 57 studies on nondiabetic individuals Diabetes Care 29 2006 2489 2497
133. S. Gawrieh, M.C. Marion, R. Komorowski, and et al. Genetic variation in the peroxisome proliferator activated receptor-gamma gene is associated with histologically advanced NAFLD Dig Dis Sci 57 2012 952 957
134. J.W. Rey, A. Noetel, A. Hardt, and et al. Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma2 in patients with fatty liver diseases World J Gastroenterol 16 2010 5830 5837
135. P. Dongiovanni, R. Rametta, A.L. Fracanzani, and et al. Lack of association between peroxisome proliferator-activated receptors alpha and gamma2 polymorphisms and progressive liver damage in patients with non-alcoholic fatty liver disease: a case control study BMC Gastroenterol 10 2010 102
136. A. Lonardo, S. Lombardini, F. Scaglioni, and et al. Hepatic steatosis and insulin resistance: does etiology make a difference? J Hepatol 44 2006 190 196
137. C. Namikawa, Z. Shu-Ping, J.R. Vyselaar, and et al. Polymorphisms of microsomal triglyceride transfer protein gene and manganese superoxide dismutase gene in non-alcoholic steatohepatitis J Hepatol 40 2004 781 786
138. S. Bernard, S. Touzet, I. Personne, and et al. Association between microsomal triglyceride transfer protein gene polymorphism and the biological features of liver steatosis in patients with type II diabetes Diabetologia 43 2000 995 999
139. C.P. Oliveira, J.T. Stefano, A.M. Cavaleiro, and et al. Association of polymorphisms of glutamate-cystein ligase and microsomal triglyceride transfer protein genes in non-alcoholic fatty liver disease J Gastroenterol Hepatol 25 2010 357 361
140. H.N. Ginsberg, N.A. Le, I.J. Goldberg, and et al. Apolipoprotein B metabolism in subjects with deficiency of apolipoproteins CIII and AI. Evidence that apolipoprotein CIII inhibits catabolism of triglyceride-rich lipoproteins by lipoprotein lipase in vivo J Clin Invest 78 1986 1287 1295
141. K.F. Petersen, S. Dufour, A. Hariri, and et al. Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease N Engl J Med 362 2010 1082 1089
142. A. Verrijken, S. Beckers, S. Francque, and et al. A gene variant of PNPLA3, but not of APOC3, is associated with histological parameters of NAFLD in an obese population Obesity (Silver Spring) 21 2013 2138 2145
143. J. Kozlitina, E. Boerwinkle, J.C. Cohen, and et al. Dissociation between APOC3 variants, hepatic triglyceride content and insulin resistance Hepatology 53 2011 467 474
144. L. Valenti, V. Nobili, A. Al-Serri, and et al. The APOC3 T-455C and C-482T promoter region polymorphisms are not associated with the severity of liver damage in patients with nonalcoholic fatty liver independently of PNPLA3 I148M genotype in patients with nonalcoholic fatty liver J Hepatol 55 2012 1409 1414
145. F. Sentinelli, S. Romeo, C. Maglio, and et al. Lack of effect of apolipoprotein C3 polymorphisms on indices of liver steatosis, lipid profile and insulin resistance in obese Southern Europeans Lipids Health Dis 10 2011 93
146. J. Grove, A.K. Daly, A.D. Burt, and et al. Heterozygotes for HFE mutations have no increased risk of advanced alcoholic liver disease Gut 43 1998 262 266
147. D.K. George, S. Goldwurm, G.A. MacDonald, and et al. Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis Gastroenterology 114 1998 311 318
148. J.E. Nelson, R. Bhattacharya, K.D. Lindor, and et al. HFE C282Y mutations are associated with advanced hepatic fibrosis in Caucasians with nonalcoholic steatohepatitis Hepatology 46 2007 723 729
149. E. Bugianesi, P. Manzini, S. D'Antico, and et al. Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver Hepatology 39 2004 179 187
150. L. Valenti, A.L. Fracanzani, E. Bugianesi, and et al. HFE genotype, parenchymal iron accumulation, and liver fibrosis in patients with nonalcoholic fatty liver disease Gastroenterology 138 2010 905 912
151. J. Raszeja-Wyszomirska, G. Kurzawski, M. Lawniczak, and et al. Nonalcoholic fatty liver disease and HFE gene mutations: a Polish study World J Gastroenterol 16 2010 2531 2536
152. A. Al-Serri, Q.M. Anstee, L. Valenti, and et al. The SOD2 C47T polymorphism influences NAFLD fibrosis severity: evidence from case-control and intra-familial allele association studies J Hepatol 56 2012 448 454
153. F. Degoul, A. Sutton, and A. Mansouri Homozygosity for alanine in the mitochondrial targeting sequence of superoxide dismutase and risk for severe alcoholic liver disease Gastroenterology 120 2001 1468 1474
154. S.F. Stewart, J.B. Leathart, Y. Chen, and et al. The valine-alanine manganese superoxide dismutase polymorphism is not associated with increased oxidative stress or susceptibility to advanced alcoholic liver disease Hepatology 36 2002 1355 1360
155. V.T. Savolainen, J. Pajarinen, and M. Perola Glutathione-S-transferase GSTM 'null' genotype and the risk of alcoholic liver disease Alcohol Clin Exp Res 20 1996 1340 1345
156. J.M. Ladero, C. Martinez, and E. Garcia-Martin Polymorphisms of the glutathione S-transferases mu-1 (GSTM1) and theta-1 (GSTT1) and the risk of advanced alcoholic liver disease Scand J Gastroenterol 40 2005 348 353
157. M. Baldini, I.C. Lohman, M. Halonen, and et al. A polymorphism in the 5'flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E Am J Respir Cell Mol Biol 20 1999 976 983
158. H.A. Jarvelainen, A. Orpana, M. Perola, and et al. Promoter polymorphism of the CD14 endotoxin receptor gene as a risk factor for alcoholic liver disease Hepatology 33 2001 1148 1153
159. J.B. Leathart, C.P. Day, and A.K. Daly No association between functional SNPs in the endotoxin receptors CD14 and TLR4 and alcoholic liver disease (ALD): is endotoxin important in the pathogenesis of ALD in humans? Hepatology 34 2001 459A
160. N.C. Arbour, E. Lorenz, and B.C. Schutte TLR4 mutations are associated with endotoxin hyporesponsiveness in humans Nat Genet 25 2000 187 191
161. C.P. Day, J. Leathart, P. McTernan, and et al. Genetic evidence for a role of gut flora in the pathogenesis of NASH in humans Hepatology 44 Suppl 1 2006 261A
162. M. Takamatsu, M. Yamauchi, Y. Maezawa, and et al. Genetic polymorphisms of interleukin-1beta in association with the development of alcoholic liver disease in Japanese patients Am J Gastroenterol 95 2000 1305 1311
163. J. Grove, A.K. Daly, and M.F. Bassendine Association of a tumor necrosis factor promoter polymorphism with susceptibility to alcoholic hepatitis Hepatology 26 1997 143 146
164. M. Vidali, S.F. Stewart, R. Rolla, and et al. Genetic and epigenetic factors in auto-immune reactions towards cytochrome P4502E1 in alcoholic liver disease Hepatology 37 2003 410 419
165. J. Grove, A.K. Daly, and M.F. Bassendine Interleukin 10 promoter region polymorphism and susceptibility to advanced alcoholic liver disease Gut 46 2000 540 545
166. R. Lazarus, W.T. Klimecki, L.J. Palmer, and et al. Single-nucleotide polymorphisms in the interleukin-10 gene: differences in frequencies, linkage disequilibrium patterns, and haplotypes in three United States ethnic groups Genomics 80 2002 223 228
167. L. Valenti, A.L. Fracanzani, P. Dongiovanni, and et al. Tumor necrosis factor alpha promoter polymorphisms and insulin resistance in nonalcoholic fatty liver disease Gastroenterology 122 2002 274 280
168. K. Tokushige, M. Takakura, N. Tsuchiya-Matsushita, and et al. Influence of TNF gene polymorphisms in Japanese patients with NASH and simple steatosis J Hepatol 46 2007 1104 1110
169. S. Petta, S. Grimaudo, C. Camma, and et al. IL28B and PNPLA3 polymorphisms affect histological liver damage in patients with non-alcoholic fatty liver disease J Hepatol 56 2012 1356 1362
170. M. Eslam, A.M. Hashem, R. Leung, and et al. Interferon-lambda rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease Nat Commun 6 2015 6422
171. M.E. Garrett, M.F. Abdelmalek, A. Ashley-Koch, and et al. IL28B rs12979860 is not associated with histologic features of NAFLD in a cohort of Caucasian North American patients J Hepatol 58 2013 402 403
172. G. Narla, A. Difeo, H.L. Reeves, and et al. A germline DNA polymorphism enhances alternative splicing of the KLF6 tumor suppressor gene and is associated with increased prostate cancer risk Cancer Res 65 2005 1213 1222
173. L. Miele, G. Beale, G. Patman, and et al. The Kruppel-like factor 6 genotype is associated with fibrosis in nonalcoholic fatty liver disease Gastroenterology 135 2008 282 291 e1
174. L.P. Bechmann, A. Gastaldelli, D. Vetter, and et al. Glucokinase links Kruppel-like factor 6 to the regulation of hepatic insulin sensitivity in nonalcoholic fatty liver disease Hepatology 55 2012 1083 1093
175. R. Bashir, C.P. Day, O.F. James, and et al. No evidence for involvement of type 1 collagen structural genes in 'genetic predisposition' to alcoholic cirrhosis J Hepatol 16 1992 316 319
176. C.H. Osterreicher, J. Halangk, T. Berg, and et al. Evaluation of the transforming growth factor beta1 codon 25 (Arg->Pro) polymorphism in alcoholic liver disease Cytokine 42 2008 18 23
177. F. Stickel, C.H. Osterreicher, J. Halangk, and et al. No role of matrixmetalloproteinase-3 genetic promoter polymorphism 1171 as a risk factor for cirrhosis in alcoholic liver disease Alcohol Clin Exp Res 32 2008 959 965
178. H. Dong, J. Wang, C. Li, and et al. The phosphatidylethanolamine N-methyltransferase gene V175M single nucleotide polymorphism confers the susceptibility to NASH in Japanese population J Hepatol 46 2007 915 920
179. J. Song, K.A. da Costa, L.M. Fischer, and et al. Polymorphism of the PEMT gene and susceptibility to nonalcoholic fatty liver disease (NAFLD) FASEB J 19 2005 1266 1271
180. L. Wang, S. Athinarayanan, G. Jiang, and et al. Fatty acid desaturase 1 gene polymorphisms control human hepatic lipid composition Hepatology 61 2015 119 128
181. A. Aravinthan, G. Mells, M. Allison, and et al. Gene polymorphisms of cellular senescence marker p21 and disease progression in non-alcohol-related fatty liver disease Cell Cycle 13 2014 1489 1494
182. S. Romeo, I. Huang-Doran, M.G. Baroni, and et al. Unravelling the pathogenesis of fatty liver disease: patatin-like phospholipase domain-containing 3 protein Curr Opin Lipidol 21 2010 247 252
183. R. Zimmermann, J.G. Strauss, G. Haemmerle, and et al. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase Science 306 2004 1383 1386
184. S. He, C. McPhaul, J.Z. Li, and et al. A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis J Biol Chem 285 2010 6706 6715
185. E.K. Speliotes, J.L. Butler, C.D. Palmer, and et al. PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease Hepatology 52 2010 904 912
186. S. Romeo, F. Sentinelli, S. Dash, and et al. Morbid obesity exposes the association between PNPLA3 I148M (rs738409) and indices of hepatic injury in individuals of European descent Int J Obes (Lond) 34 2010 190 194
187. Y. Huang, J.C. Cohen, and H.H. Hobbs Expression and characterization of a PNPLA3 protein isoform (I148M) associated with nonalcoholic fatty liver disease J Biol Chem 286 2011 37085 37093
188. C. Pirazzi, M. Adiels, M.A. Burza, and et al. Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) affects hepatic VLDL secretion in humans and in vitro J Hepatol 57 2012 1276 1282
189. C.M. Jenkins, D.J. Mancuso, W. Yan, and et al. Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities J Biol Chem 279 2004 48968 48975
190. M. Kumari, G. Schoiswohl, C. Chitraju, and et al. Adiponutrin functions as a nutritionally regulated lysophosphatidic acid acyltransferase Cell Metab 15 2012 691 702
191. W. Chen, B. Chang, L. Li, and et al. Patatin-like phospholipase domain-containing 3/adiponutrin deficiency in mice is not associated with fatty liver disease Hepatology 52 2010 1134 1142
192. M.K. Basantani, M.T. Sitnick, L. Cai, and et al. Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome J Lipid Res 52 2011 318 329
193. J.Z. Li, Y. Huang, R. Karaman, and et al. Chronic overexpression of PNPLA3I148M in mouse liver causes hepatic steatosis J Clin Invest 122 2012 4130 4144
194. E. Smagris, S. BasuRay, J. Li, and et al. Pnpla3I148M knockin mice accumulate PNPLA3 on lipid droplets and develop hepatic steatosis Hepatology 61 2015 108 118
195. C. Pirazzi, L. Valenti, B.M. Motta, and et al. PNPLA3 has retinyl-palmitate lipase activity in human hepatic stellate cells Hum Mol Genet 23 2014 4077 4085
196. M. Kovarova, I. Konigsrainer, A. Konigsrainer, and et al. The genetic variant I148M in PNPLA3 is associated with increased hepatic retinyl-palmitate storage in humans J Clin Endocrinol Metab 100 2015 E1568 E1574
197. A. Mondul, R.M. Mancina, A. Merlo, and et al. PNPLA3 I148M variant influences circulating retinol in adults with nonalcoholic fatty liver disease or obesity J Nutr 145 2015 1687 1691
198. L. Carim-Todd, M. Escarceller, X. Estivill, and et al. Cloning of the novel gene TM6SF1 reveals conservation of clusters of paralogous genes between human chromosomes 15q24 - >q26 and 19p13.3 - >p12 Cytogenet Cell Genet 90 2000 255 260
199. I. Surakka, M. Horikoshi, R. Magi, and et al. The impact of low-frequency and rare variants on lipid levels Nat Genet 47 2015 589 597
200. O.L. Holmen, H. Zhang, Y. Fan, and et al. Systematic evaluation of coding variation identifies a candidate causal variant in TM6SF2 influencing total cholesterol and myocardial infarction risk Nat Genet 46 2014 345 351
201. Y. Zhou, G. Llaurado, M. Oresic, and et al. Circulating triacylglycerol signatures and insulin sensitivity in NAFLD associated with the E167K variant in TM6SF2 J Hepatol 62 2015 657 663
202. G. Musso, R. Gambino, M. Cassader, and et al. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity Ann Med 43 2011 617 649
203. T. Kitamoto, A. Kitamoto, Y. Ogawa, and et al. Targeted-bisulfite sequence analysis of the methylation of CpG islands in genes encoding PNPLA3, SAMM50, and PARVB of patients with non-alcoholic fatty liver disease J Hepatol 63 2015 494 502
204. S. Bala, M. Marcos, K. Kodys, and et al. Up-regulation of microRNA-155 in macrophages contributes to increased tumor necrosis factor {alpha} (TNF{alpha}) production via increased mRNA half-life in alcoholic liver disease J Biol Chem 286 2011 1436 1444
205. S. Bala, and G. Szabo MicroRNA signature in alcoholic liver disease Int J Hepatol 2012 2012 498232
206. R.P. Dippold, R. Vadigepalli, G.E. Gonye, and et al. Chronic ethanol feeding enhances miR-21 induction during liver regeneration while inhibiting proliferation in rats Am J Physiol Gastrointest Liver Physiol 303 2012 G733 G743
207. R. Lakshman, R. Shah, K. Reyes-Gordillo, and et al. Synergy between NAFLD and AFLD and potential biomarkers Clin Res Hepatol Gastroenterol 39 Suppl 1 2015 S29 S34
208. P. Cordero, J. Campion, F.I. Milagro, and et al. Transcriptomic and epigenetic changes in early liver steatosis associated to obesity: effect of dietary methyl donor supplementation Mol Genet Metab 110 2013 388 395
209. O. Khalid, J.J. Kim, H.S. Kim, and et al. Gene expression signatures affected by alcohol-induced DNA methylomic deregulation in human embryonic stem cells Stem Cell Res 12 2014 791 806
210. M. Zeybel, T. Hardy, Y.K. Wong, and et al. Multigenerational epigenetic adaptation of the hepatic wound-healing response Nat Med 18 2012 1369 1377
211. M. Zeybel, T. Hardy, S.M. Robinson, and et al. Differential DNA methylation of genes involved in fibrosis progression in non-alcoholic fatty liver disease and alcoholic liver disease Clin Epigenetics 7 2015 25
212. E. Scorletti, A.L. West, L. Bhatia, and et al. Treating liver fat and serum triglyceride levels in NAFLD, effects of PNPLA3 and TM6SF2 genotypes: results from the WELCOME trial J Hepatol 63 2015 1476 1483
213. P. Dongiovanni, S. Petta, V. Mannisto, and et al. Statin use and non-alcoholic steatohepatitis in at risk individuals J Hepatol 63 2015 705 712
214. X. Yuan, D. Waterworth, J.R. Perry, and et al. Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes Am J Hum Genet 83 2008 520 528
215. J.C. Chambers, W. Zhang, J. Sehmi, and et al. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma Nat Genet 43 2011 1131 1138
216. T. Kitamoto, A. Kitamoto, M. Yoneda, and et al. Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB genes are associated with development and progression of nonalcoholic fatty liver disease in Japan Hum Genet 132 2013 783 792
217. P. Couzigou, C. Coutelle, B. Fleury, and et al. Alcohol and aldehyde dehydrogenase genotypes, alcoholism and alcohol related disease Alcohol Alcohol Suppl 2 1994 21 27
218. Y.C. Chao, M.F. Wang, H.S. Tang, and et al. Genotyping of alcohol dehydrogenase at the ADH2 and ADH3 loci by using a polymerase chain reaction and restriction-fragment-length polymorphism in Chinese alcoholic cirrhotics and non-alcoholics Proc Natl Sci Counc Repub China B 18 1994 101 106
219. D.I. Sherman, R.J. Ward, M. Warren-Perry, and et al. Association of restriction fragment length polymorphism in alcohol dehydrogenase 2 gene with alcohol induced liver damage BMJ 307 1993 1388 1390
220. F. Tanaka, Y. Shiratori, O. Yokosuka, and et al. High incidence of ADH2∗1/ALDH2∗1 genes among Japanese alcohol dependents and patients with alcoholic liver disease Hepatology 23 1996 234 239
221. A. Monzoni, F. Masutti, G. Saccoccio, and et al. Genetic determinants of ethanol-induced liver damage Mol Med 7 2001 255 262
222. G. Musso, R. Gambino, G. Pacini, and et al. Transcription factor 7-like 2 polymorphism modulates glucose and lipid homeostasis, adipokine profile, and hepatocyte apoptosis in NASH Hepatology 49 2009 426 435
223. V.T. Savolainen, J. Pjarinen, M. Perola, and et al. Glutathione-S-transferase GST M1 "null" genotype and the risk of alcoholic liver disease Alcohol Clin Exp Res 20 1996 1340 1345
224. A.M. Brind, A. Hurlstone, D. Edrisinghe, and et al. The role of polymorphisms of glutathione S-transferases GSTM1, M3, P1, T1 and A1 in susceptibility to alcoholic liver disease Alcohol Alcohol 39 2004 478 483
225. S. Buch, C. Schafmayer, H. Volzke, and et al. A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease Nat Genet 39 2007 995 999
226. S.F. Stewart, J.B. Leathart, Y. Chen, and et al. Valine-alanine manganese superoxide dismutase polymorphism is not associated with alcohol-induced oxidative stress or liver fibrosis Hepatology 36 2002 1355 1360
227. R. Fares, S. Petta, R. Lombardi, and et al. The UCP2 -866 G>A promoter region polymorphism is associated with nonalcoholic steatohepatitis Liver Int 35 2015 1574 1580
228. K.S. Vimaleswaran, A. Cavadino, N. Verweij, and et al. Interactions between uncoupling protein 2 gene polymorphisms, obesity and alcohol intake on liver function: a large meta-analysed population-based study Eur J Endocrinol 173 2015 863 872
229. J. Grove, A.K. Daly, M.F. Bassendine, and et al. Association of a tumor necrosis factor promoter polymorphism with susceptibility to alcoholic steatohepatitis Hepatology 26 1997 143 146
230. I.J. Pastor, F.J. Laso, A. Romero, and et al. -238 G>A polymorphism of tumor necrosis factor alpha gene (TNFA) is associated with alcoholic liver cirrhosis in alcoholic Spanish men Alcohol Clin Exp Res 29 2005 1928 1931
231. M. Marcos, M. Gomez-Munuera, I. Pastor, and et al. Tumor necrosis factor polymorphisms and alcoholic liver disease: a HuGE review and meta-analysis Am J Epidemiol 170 2009 948 956
232. J. Grove, A.K. Daly, M.F. Bassendine, and et al. Interleukin 10 promoter region polymorphisms and susceptibility to advanced alcoholic liver disease Gut 46 2000 540 545
233. J.B. Leathart, C.P. Day, and A.K. Daly No association between functional SNPs in the endotoxin receptors CD14 and TLR4 and alcoholic liver disease (ALD): is endotoxin important in the pathogenesis of aid in humans? Hepatology 34 2001 459a
234. L. Valenti, T. De Feo, A.L. Fracanzani, and et al. Cytotoxic T-lymphocyte antigen-4 A49G polymorphism is associated with susceptibility to and severity of alcoholic liver disease in Italian patients Alcohol Alcohol 39 2004 276 280
235. J. Guo, J. Loke, F. Zheng, and et al. Functional linkage of cirrhosis-predictive single nucleotide polymorphisms of Toll-like receptor 4 to hepatic stellate cell responses Hepatology 49 2009 960 968
236. H. Huang, M.L. Shiffman, S. Friedman, and et al. A 7 gene signature identifies the risk of developing cirrhosis in patients with chronic hepatitis C Hepatology 46 2007 297 306
237. A. Spruss, G. Kanuri, S. Wagnerberger, and et al. Toll-like receptor 4 is involved in the development of fructose-induced hepatic steatosis in mice Hepatology 50 2009 1094 1104
238. A. Auinger, L. Valenti, M. Pfeuffer, and et al. A promoter polymorphism in the liver-specific fatty acid transport protein 5 is associated with features of the metabolic syndrome and steatosis Horm Metab Res 42 2010 854 859
239. D. Hirsch, A. Stahl, and H.F. Lodish A family of fatty acid transporters conserved from mycobacterium to man Proc Natl Acad Sci U S A 95 1998 8625 8629
240. H. Doege, D. Grimm, A. Falcon, and et al. Silencing of hepatic fatty acid transporter protein 5 in vivo reverses diet-induced non-alcoholic fatty liver disease and improves hyperglycemia J Biol Chem 283 2008 22186 22192
241. L. Valenti, B.M. Motta, A. Alisi, and et al. LPIN1 rs13412852 polymorphism in pediatric nonalcoholic fatty liver disease J Pediatr Gastroenterol Nutr 54 2012 588 593
242. K. Reue, and P. Zhang The lipin protein family: dual roles in lipid biosynthesis and gene expression FEBS Lett 582 2008 90 96
243. K. Reue The lipin family: mutations and metabolism Curr Opin Lipidol 20 2009 165 170
244. S. Sookoian, G.O. Castano, A.L. Burgueno, and et al. The nuclear receptor PXR gene variants are associated with liver injury in nonalcoholic fatty liver disease Pharmacogenet Genomics 20 2010 1 8
245. B. Zhang, W. Xie, and M.D. Krasowski PXR: a xenobiotic receptor of diverse function implicated in pharmacogenetics Pharmacogenomics 9 2008 1695 1709
246. J. Zhou, Y. Zhai, Y. Mu, and et al. A novel pregnane X receptor-mediated and sterol regulatory element-binding protein-independent lipogenic pathway J Biol Chem 281 2006 15013 15020
247. S. Chen, Y. Li, S. Li, and et al. A Val227Ala substitution in the peroxisome proliferator activated receptor alpha (PPAR alpha) gene associated with non-alcoholic fatty liver disease and decreased waist circumference and waist-to-hip ratio J Gastroenterol Hepatol 23 2008 1415 1418
248. K. Yamakawa-Kobayashi, H. Ishiguro, T. Arinami, and et al. A Val227Ala polymorphism in the peroxisome proliferator activated receptor alpha (PPARalpha) gene is associated with variations in serum lipid levels J Med Genet 39 2002 189 191
249. H. Kim, M. Haluzik, Z. Asghar, and et al. Peroxisome proliferator-activated receptor-alpha agonist treatment in a transgenic model of type 2 diabetes reverses the lipotoxic state and improves glucose homeostasis Diabetes 52 2003 1770 1778
250. M.D. Demirag, H.I. Onen, M.Y. Karaoguz, and et al. Apolipoprotein E gene polymorphism in nonalcoholic fatty liver disease Dig Dis Sci 52 2007 3399 3403
251. A. Sazci, G. Akpinar, C. Aygun, and et al. Association of apolipoprotein E polymorphisms in patients with non-alcoholic steatohepatitis Dig Dis Sci 53 2008 3218 3224
252. F. Stickel, and J. Hampe Genetic determinants of alcoholic liver disease Gut 61 2012 150 159
253. M. Yoneda, K. Hotta, Y. Nozaki, and et al. Association between angiotensin II type 1 receptor polymorphisms and the occurrence of nonalcoholic fatty liver disease Liver Int 29 2009 1078 1085
254. S.M. Zain, Z. Mohamed, S. Mahadeva, and et al. Susceptibility and gene interaction study of the angiotensin II type 1 receptor (AGTR1) gene polymorphisms with non-alcoholic fatty liver disease in a multi-ethnic population PLoS One 8 2013 e58538