The nuclear receptor PXR gene variants are associated with liver injury in nonalcoholic fatty liver disease

Pharmacogenetics and Genomics

Volumn 20, Issue 1, 2010, Pages 1-8

  Sookoian, Silvia ^a,b   Castaño, Gustavo O ^b   Burgueño, Adriana L ^a   Gianotti, Tomas Fernández ^a   Rosselli, María Soledad ^a   Pirola, Carlos Jose ^a  

^a INSTITUTO DE INVESTIGACIONES MÉDICAS ALFREDO LANARI   (Argentina)

^b Hospital General de Agudos Dr Abel Zubizarreta   (Argentina)

Author keywords

Gene variant; NASH; Nonalcoholic steatohepatitis; NR1I2; Nuclear receptors; PAR; Xenobiotic

Indexed keywords

ALANINE AMINOTRANSFERASE; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; GAMMA GLUTAMYLTRANSFERASE; PREGNANE X RECEPTOR;

ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALKALINE PHOSPHATASE BLOOD LEVEL; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; CASE CONTROL STUDY; CHROMOSOME 3; CONTROLLED STUDY; DISEASE ASSOCIATION; DISEASE SEVERITY; FEMALE; GAMMA GLUTAMYL TRANSFERASE BLOOD LEVEL; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENOTYPE; HAPLOTYPE; HUMAN; HUMAN TISSUE; LIVER BIOPSY; LIVER INJURY; MAJOR CLINICAL STUDY; MALE; NONALCOHOLIC FATTY LIVER; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM;

CASE-CONTROL STUDIES; CROSS-SECTIONAL STUDIES; DRUG-INDUCED LIVER INJURY; FATTY LIVER; FEMALE; GENETIC ASSOCIATION STUDIES; GENOTYPE; HAPLOTYPES; HUMANS; LIVER; MALE; MIDDLE AGED; POLYMORPHISM, SINGLE NUCLEOTIDE; RECEPTORS, STEROID;

EID: 73949117713     PISSN: 17446872     EISSN: 17446880     Source Type: Journal    
DOI: 10.1097/FPC.0b013e328333a1dd     Document Type: Article

References (92)

1. Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004; 40:1387-1395.
2. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002; 346: 1221-1231.
3. Ekstedt M, Franzen LE, Mathiesen UL,Thorelius L, Holmqvist M, Bodemar G, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006; 44:865-873.
4. Adams LA, Sanderson S, Lindor KD, Angulo P. The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol 2005; 42:132-138.
5. Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 1999; 30:1356-1362.
6. Fracanzani AL, Valenti L, Bugianesi E, Andreoletti M, Colli A, Vanni E, et al. Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes. Hepatology 2008; 48:792-798.
7. Merriman RB, Aouizerat BE, Bass NM. Genetic influences in nonalcoholic fatty liver disease. J Clin Gastroenterol 2006; 40:S30-S33.
8. Sookoian S, Castano G, Gianotti TF, Gemma C, Pirola CJ. Polymorphisms of MRP2 (ABCC2) are associated with susceptibility to nonalcoholic fatty liver disease. J Nutr Biochem 2009; 20:765-770.
9. Sookoian S, Gemma C, Gianotti TF, Burgueno A, Castano G, Pirola CJ. Genetic variants of Clock transcription factor are associated with individual susceptibility to obesity. Am J Clin Nutr 2008; 87:1606-1615.
10. Sookoian S, Castano G, Gianotti TF, Gemma C, Rosselli MS, Pirola CJ. Genetic variants in STAT3 are associated with nonalcoholic fatty liver disease. Cytokine 2008; 44:201-206.
11. Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008; 40:1461-1465.
12. Sookoian S, Castano GO, Burgueno AL, Fernandez GT, Rosselli MS, Pirola CJ. A nonsynonymous gene variant in adiponutrin gene is associated with nonalcoholic fatty liver disease severity. J Lipid Res 2009; 50:2111-2116.
13. Cave M, Deaciuc I, Mendez C, Song Z, Joshi-Barve S, Barve S, et al. Nonalcoholic fatty liver disease: predisposing factors and the role of nutrition. J Nutr Biochem 2007; 18:184-195.
14. Bergheim I, Weber S, Vos M, Kramer S, Volynets V, Kaserouni S, et al. Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: role of endotoxin. J Hepatol 2008; 48:983-992.
15. Sugatani J, Wada T, Osabe M, Yamakawa K, Yoshinari K, Miwa M. Dietary inulin alleviates hepatic steatosis and xenobiotics-induced liver injury in rats fed a high-fat and high-sucrose diet: association with the suppression of hepatic cytochrome P450 and hepatocyte nuclear factor 4alpha expression. Drug Metab Dispos 2006; 34:1677-1687.
16. Weltman MD, Farrell GC, Liddle C. Increased hepatocyte CYP2E1 expression in a rat nutritional model of hepatic steatosis with inflammation. Gastroenterology 1996; 111:1645-1653.
17. Wei Y, Wang D, Topczewski F, Pagliassotti MJ. Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells. Am J Physiol Endocrinol Metab 2006; 291:E275-E281. (Pubitemid 44035286)
18. Malhi H, Barreyro FJ, Isomoto H, Bronk SF, Gores GJ. Free fatty acids sensitise hepatocytes to TRAIL mediated cytotoxicity. Gut 2007; 56:1124-1131.
19. Kliewer SA, Goodwin B, Willson TM. The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism. Endocr Rev 2002; 23:687-702.
20. Zhang B, Xie W, Krasowski MD. PXR: a xenobiotic receptor of diverse function implicated in pharmacogenetics. Pharmacogenomics 2008; 9:1695-1709.
21. Zhou J, Zhai Y, Mu Y, Gong H, Uppal H, Toma D, et al. A novel pregnane X receptor-mediated and sterol regulatory element-binding protein-independent lipogenic pathway. J Biol Chem 2006; 281:15013-15020.
22. Zhou J, Febbraio M, Wada T, Zhai Y, Kuruba R, He J, et al. Hepatic fatty acid transporter Cd36 is a common target of LXR, PXR, and PPAR gamma in promoting steatosis. Gastroenterology 2008; 134:556-567.
23. Mendler MH, Bouillet P, Le Sidaner A, Lavoine E, Labrousse F, Sautereau D, et al. Dual-energy CT in the diagnosis and quantification of fatty liver: limited clinical value in comparison to ultrasound scan and single-energy CT, with special reference to iron overload. J Hepatol 1998; 28:785-794.
24. Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 1999; 94:2467-2474.
25. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003; 37:1202-1219.
26. Kawasaki ES. Sample preparation from blood, cells, and other fluids. In: Innis MA, Gelfand DH, Sninsky JJ, White TJ, editors. PCR Protocols. A guide to Methods and Applications. San Diego: Academic Press, INC.; 1990 pp. 146-152.
27. De Bakker PI, Yelensky R, Pe'er I, Gabriel SB, Daly MJ, Altshuler D. Efficiency and power in genetic association studies. Nat Genet 2005; 37:1217-1223.
28. Lamba J, Lamba V, Strom S, Venkataramanan R, Schuetz E. Novel single nucleotide polymorphisms in the promoter and intron 1 of human pregnane X receptor/NR1I2 and their association with CYP3A4 expression. Drug Metab Dispos 2008; 36:169-181.
29. Zhang J, Kuehl P, Green ED, Touchman JW, Watkins PB, Daly A, et al. The human pregnane X receptor: genomic structure and identification and functional characterization of natural allelic variants. Pharmacogenetics 2001; 11:555-572.
30. Hustert E, Zibat A, Presecan-Siedel E, Eiselt R, Mueller R, Fuss C, et al. Natural protein variants of pregnane X receptor with altered transactivation activity toward CYP3A4. Drug Metab Dispos 2001; 29:1454-1459.
31. Myakishev MV, Khripin Y, Hu S, Hamer DH. High-throughput SNP genotyping by allele-specific PCR with universal energy-transfer-labeled primers. Genome Res 2001; 11:163-169.
32. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007; 81:559-575.
33. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005; 21:263-265.
34. Carter KW, McCaskie PA, Palmer LJ. SimHap GUI: An intuitive graphical user interface for genetic association analysis. BMC Bioinformatics 2008; 9:557.
35. Pritchard JK, Stephens M, Donnelly P. Inference of population structure using multilocus genotype data. Genetics 2000; 155:945-959.
36. Skol AD, Scott LJ, Abecasis GR, Boehnke M. Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies. Nat Genet 2006; 38:209-213.
37. Greenfield V, Cheung O, Sanyal AJ. Recent advances in nonalcoholic fatty liver disease. Curr Opin Gastroenterol 2008; 24:320-327.
38. Tuomisto TT, Riekkinen MS, Viita H, Levonen AL, Yla-Herttuala S. Analysis of gene and protein expression during monocyte-macrophage differentiation and cholesterol loading-cDNA and protein array study. Atherosclerosis 2005; 180:283-291.
39. Fernandez-Real JM, Handberg A, Ortega F, Hoejlund K, Vendrell J, Ricart W. Circulating soluble CD36 is a novel marker of liver injury in subjects with altered glucose tolerance. J Nutr Biochem 2008; 20:477-484.
40. Konno Y, Negishi M, Kodama S. The roles of nuclear receptors CAR and PXR in hepatic energy metabolism. Drug Metab Pharmacokinet 2008; 23:8-13.
41. Kakizaki S, Yamazaki Y, Takizawa D, Negishi M. New insights on the xenobiotic-sensing nuclear receptors in liver diseases-CAR and PXR-. Curr Drug Metab 2008; 9:614-621.
42. Day CP, James OF. Steatohepatitis: a tale of two hits? Gastroenterology 1998; 114:842-845.
43. Tirona RG, Lee W, Leake BF, Lan LB, Cline CB, Lamba V, et al. The orphan nuclear receptor HNF4alpha determines PXR-and CAR-mediated xenobiotic induction of CYP3A4. Nat Med 2003; 9:220-224.
44. Cadranel JF, Rufat P, Degos F. Practices of liver biopsy in France: results of a prospective nationwide survey. For the Group of Epidemiology of the French Association for the study of the liver (AFEF). Hepatology 2000; 32:477-481.
45. Nannipieri M, Gonzales C, Baldi S, Posadas R, Williams K, Haffner SM, et al. Liver enzymes, the metabolic syndrome, and incident diabetes: the Mexico City Diabetes Study. Diabetes Care 2005; 28:1757-1762.
46. Lee DS, Evans JC, Robins SJ, Wilson PW, Albano I, Fox CS, et al. Gamma glutamyl transferase and metabolic syndrome, cardiovascular disease, and mortality risk: the Framingham Heart Study. Arterioscler Thromb Vasc Biol 2007; 27:127-133.
47. Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004; 40:1387-1395.
48. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002; 346: 1221-1231.
49. Ekstedt M, Franzen LE, Mathiesen UL,Thorelius L, Holmqvist M, Bodemar G, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006; 44:865-873.
50. Adams LA, Sanderson S, Lindor KD, Angulo P. The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol 2005; 42:132-138.
51. Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 1999; 30:1356-1362.
52. Fracanzani AL, Valenti L, Bugianesi E, Andreoletti M, Colli A, Vanni E, et al. Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes. Hepatology 2008; 48:792-798.
53. Merriman RB, Aouizerat BE, Bass NM. Genetic influences in nonalcoholic fatty liver disease. J Clin Gastroenterol 2006; 40:S30-S33.
54. Sookoian S, Castano G, Gianotti TF, Gemma C, Pirola CJ. Polymorphisms of MRP2 (ABCC2) are associated with susceptibility to nonalcoholic fatty liver disease. J Nutr Biochem 2009; 20:765-770.
55. Sookoian S, Gemma C, Gianotti TF, Burgueno A, Castano G, Pirola CJ. Genetic variants of Clock transcription factor are associated with individual susceptibility to obesity. Am J Clin Nutr 2008; 87:1606-1615.
56. Sookoian S, Castano G, Gianotti TF, Gemma C, Rosselli MS, Pirola CJ. Genetic variants in STAT3 are associated with nonalcoholic fatty liver disease. Cytokine 2008; 44:201-206.
57. Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008; 40:1461-1465.
58. Sookoian S, Castano GO, Burgueno AL, Fernandez GT, Rosselli MS, Pirola CJ. A nonsynonymous gene variant in adiponutrin gene is associated with nonalcoholic fatty liver disease severity. J Lipid Res 2009; 50:2111-2116.
59. Cave M, Deaciuc I, Mendez C, Song Z, Joshi-Barve S, Barve S, et al. Nonalcoholic fatty liver disease: predisposing factors and the role of nutrition. J Nutr Biochem 2007; 18:184-195.
60. Bergheim I, Weber S, Vos M, Kramer S, Volynets V, Kaserouni S, et al. Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: role of endotoxin. J Hepatol 2008; 48:983-992.
61. Sugatani J, Wada T, Osabe M, Yamakawa K, Yoshinari K, Miwa M. Dietary inulin alleviates hepatic steatosis and xenobiotics-induced liver injury in rats fed a high-fat and high-sucrose diet: association with the suppression of hepatic cytochrome P450 and hepatocyte nuclear factor 4alpha expression. Drug Metab Dispos 2006; 34:1677-1687.
62. Weltman MD, Farrell GC, Liddle C. Increased hepatocyte CYP2E1 expression in a rat nutritional model of hepatic steatosis with inflammation. Gastroenterology 1996; 111:1645-1653.
63. Wei Y, Wang D, Topczewski F, Pagliassotti MJ. Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells. Am J Physiol Endocrinol Metab 2006; 291:E275-E281. (Pubitemid 44035286)
64. Malhi H, Barreyro FJ, Isomoto H, Bronk SF, Gores GJ. Free fatty acids sensitise hepatocytes to TRAIL mediated cytotoxicity. Gut 2007; 56:1124-1131.
65. Kliewer SA, Goodwin B, Willson TM. The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism. Endocr Rev 2002; 23:687-702.
66. Zhang B, Xie W, Krasowski MD. PXR: a xenobiotic receptor of diverse function implicated in pharmacogenetics. Pharmacogenomics 2008; 9:1695-1709.
67. Zhou J, Zhai Y, Mu Y, Gong H, Uppal H, Toma D, et al. A novel pregnane X receptor-mediated and sterol regulatory element-binding protein-independent lipogenic pathway. J Biol Chem 2006; 281:15013-15020.
68. Zhou J, Febbraio M, Wada T, Zhai Y, Kuruba R, He J, et al. Hepatic fatty acid transporter Cd36 is a common target of LXR, PXR, and PPAR gamma in promoting steatosis. Gastroenterology 2008; 134:556-567.
69. Mendler MH, Bouillet P, Le Sidaner A, Lavoine E, Labrousse F, Sautereau D, et al. Dual-energy CT in the diagnosis and quantification of fatty liver: limited clinical value in comparison to ultrasound scan and single-energy CT, with special reference to iron overload. J Hepatol 1998; 28:785-794.
70. Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 1999; 94:2467-2474.
71. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003; 37:1202-1219.
72. Kawasaki ES. Sample preparation from blood, cells, and other fluids. In: Innis MA, Gelfand DH, Sninsky JJ, White TJ, editors. PCR Protocols. A guide to Methods and Applications. San Diego: Academic Press, INC.; 1990 pp. 146-152.
73. De Bakker PI, Yelensky R, Peer I, Gabriel SB, Daly MJ, Altshuler D. Efficiency and power in genetic association studies. Nat Genet 2005; 37:1217-1223.
74. Lamba J, Lamba V, Strom S, Venkataramanan R, Schuetz E. Novel single nucleotide polymorphisms in the promoter and intron 1 of human pregnane X receptor/NR1I2 and their association with CYP3A4 expression. Drug Metab Dispos 2008; 36:169-181.
75. Zhang J, Kuehl P, Green ED, Touchman JW, Watkins PB, Daly A, et al. The human pregnane X receptor: genomic structure and identification and functional characterization of natural allelic variants. Pharmacogenetics 2001; 11:555-572.
76. Hustert E, Zibat A, Presecan-Siedel E, Eiselt R, Mueller R, Fuss C, et al. Natural protein variants of pregnane X receptor with altered transactivation activity toward CYP3A4. Drug Metab Dispos 2001; 29:1454-1459.
77. Myakishev MV, Khripin Y, Hu S, Hamer DH. High-throughput SNP genotyping by allele-specific PCR with universal energy-transfer-labeled primers. Genome Res 2001; 11:163-169.
78. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007; 81:559-575.
79. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005; 21:263-265.
80. Carter KW, McCaskie PA, Palmer LJ. SimHap GUI: An intuitive graphical user interface for genetic association analysis. BMC Bioinformatics 2008; 9:557.
81. Pritchard JK, Stephens M, Donnelly P. Inference of population structure using multilocus genotype data. Genetics 2000; 155:945-959.
82. Skol AD, Scott LJ, Abecasis GR, Boehnke M. Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies. Nat Genet 2006; 38:209-213.
83. Greenfield V, Cheung O, Sanyal AJ. Recent advances in nonalcoholic fatty liver disease. Curr Opin Gastroenterol 2008; 24:320-327.
84. Tuomisto TT, Riekkinen MS, Viita H, Levonen AL, Yla-Herttuala S. Analysis of gene and protein expression during monocyte-macrophage differentiation and cholesterol loading-cDNA and protein array study. Atherosclerosis 2005; 180:283-291.
85. Fernandez-Real JM, Handberg A, Ortega F, Hoejlund K, Vendrell J, Ricart W. Circulating soluble CD36 is a novel marker of liver injury in subjects with altered glucose tolerance. J Nutr Biochem 2008; 20:477-484.
86. Konno Y, Negishi M, Kodama S. The roles of nuclear receptors CAR and PXR in hepatic energy metabolism. Drug Metab Pharmacokinet 2008; 23:8-13.
87. Kakizaki S, Yamazaki Y, Takizawa D, Negishi M. New insights on the xenobiotic-sensing nuclear receptors in liver diseases-CAR and PXR-. Curr Drug Metab 2008; 9:614-621.
88. Day CP, James OF. Steatohepatitis: a tale of two hits? Gastroenterology 1998; 114:842-845.
89. Tirona RG, Lee W, Leake BF, Lan LB, Cline CB, Lamba V, et al. The orphan nuclear receptor HNF4alpha determines PXR- and CAR-mediated xenobiotic induction of CYP3A4. Nat Med 2003; 9:220-224.
90. Cadranel JF, Rufat P, Degos F. Practices of liver biopsy in France: results of a prospective nationwide survey. For the Group of Epidemiology of the French Association for the study of the liver (AFEF). Hepatology 2000; 32:477-481.
91. Nannipieri M, Gonzales C, Baldi S, Posadas R, Williams K, Haffner SM, et al. Liver enzymes, the metabolic syndrome, and incident diabetes: the Mexico City Diabetes Study. Diabetes Care 2005; 28:1757-1762.
92. Lee DS, Evans JC, Robins SJ, Wilson PW, Albano I, Fox CS, et al. Gamma glutamyl transferase and metabolic syndrome, cardiovascular disease, and mortality risk: the Framingham Heart Study. Arterioscler Thromb Vasc Biol 2007; 27:127-133.