PNPLA3 I148M variant and hepatocellular carcinoma: A common genetic variant for a rare disease

Digestive and Liver Disease

Volumn 45, Issue 8, 2013, Pages 619-624

  Valenti, Luca ^a   Dongiovanni, Paola ^a   Ginanni Corradini, Stefano ^b   Burza, Maria Antonella ^c   Romeo, Stefano ^c,d  

^a UNIVERSITY OF MILAN   (Italy)

^b SAPIENZA UNIVERSITY OF ROME   (Italy)

^c UNIVERSITY OF GOTHENBURG   (Sweden)

^d UNIVERSITY MAGNA GRAECIA OF CATANZARO   (Italy)

Author keywords

Hepatocellular carcinoma; Human genetics; Patatin like phospholipase domain containing 3

Indexed keywords

ISOLEUCINE; MEMBRANE PROTEIN; METHIONINE; PNPLA3 PROTEIN; UNCLASSIFIED DRUG;

CANCER GENETICS; CARCINOGENIC ACTIVITY; DISEASE PREDISPOSITION; GAIN OF FUNCTION MUTATION; GENE EXPRESSION; GENETIC ASSOCIATION; GENETIC VARIABILITY; HUMAN; LIVER CELL CARCINOMA; LOSS OF FUNCTION MUTATION; MOLECULAR GENETICS; NONHUMAN; PRIORITY JOURNAL; RARE DISEASE; REVIEW; THEORY;

HEPATOCELLULAR CARCINOMA; HUMAN GENETICS; PATATIN-LIKE PHOSPHOLIPASE DOMAIN CONTAINING 3;

CARCINOMA, HEPATOCELLULAR; FATTY LIVER; GENETIC MARKERS; HEPATITIS, CHRONIC; HUMANS; LIPASE; LIVER CIRRHOSIS; LIVER NEOPLASMS; MEMBRANE PROTEINS; MUTATION; POLYMORPHISM, SINGLE NUCLEOTIDE; PREDICTIVE VALUE OF TESTS; RARE DISEASES; RISK FACTORS; SENSITIVITY AND SPECIFICITY; SEVERITY OF ILLNESS INDEX;

EID: 84881559322     PISSN: 15908658     EISSN: 18783562     Source Type: Journal    
DOI: 10.1016/j.dld.2012.12.006     Document Type: Review

References (73)

1. Parkin D.M., Bray F., Ferlay J., et al. Global cancer statistics, 2002. CA: A Cancer Journal for Clinicians 2005, 55:74-108.
2. European Association for the Study of the Liver; European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. Journal of Hepatology 2012;56:908-43.
3. Fracanzani A.L., Fargion S., Stazi M.A., et al. Association between heterozygosity for HFE gene mutations and hepatitis viruses in hepatocellular carcinoma. Blood Cells, Molecules, and Diseases 2005, 35:27-32.
4. Rudnick D.A., Perlmutter D.H. Alpha-1-antitrypsin deficiency: a new paradigm for hepatocellular carcinoma in genetic liver disease. Hepatology 2005, 42:514-521.
5. Fracanzani A.L., Piperno A., Valenti L., et al. Hemochromatosis in Italy in the last 30 years: role of genetic and acquired factors. Hepatology 2010, 51:501-510.
6. Baffy G., Brunt E.M., Caldwell S.H. Hepatocellular carcinoma in non-alcoholic fatty liver disease: an emerging menace. Journal of Hepatology 2012, 56:1384-1391.
7. Nahon P., Zucman-Rossi J. Single nucleotide polymorphisms and risk of hepatocellular carcinoma in cirrhosis. Journal of Hepatology 2012.
8. Jin F., Xiong W.J., Jing J.C., et al. Evaluation of the association studies of single nucleotide polymorphisms and hepatocellular carcinoma: a systematic review. Journal of Cancer Research and Clinical Oncology 2011, 137:1095-1104.
9. Romeo S., Kozlitina J., Xing C., et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nature Genetics 2008, 40:1461-1465.
10. Yuan X., Waterworth D., Perry J.R., et al. Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes. American Journal of Human Genetics 2008, 83:520-528.
11. Wagenknecht L.E., Palmer N.D., Bowden D.W., et al. Association of PNPLA3 with non-alcoholic fatty liver disease in a minority cohort: the Insulin Resistance Atherosclerosis Family Study. Liver International 2011, 31:412-416.
12. Trepo E., Guyot E., Ganne-Carrie N., et al. PNPLA3 (rs738409 C>G) is a common risk variant associated with hepatocellular carcinoma in alcoholic cirrhosis. Hepatology 2012, 55:1307-1308.
13. Nischalke H.D., Berger C., Luda C., 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 2012, 6:e27087.
14. Falleti E., Fabris C., Cmet S., et al. PNPLA3 rs738409C/G polymorphism in cirrhosis: relationship with the aetiology of liver disease and hepatocellular carcinoma occurrence. Liver International 2012, 31:1137-1143.
15. Burza M.A., Pirazzi C., Maglio C., et al. PNPLA3 I148M (rs738409) genetic variant is associated with hepatocellular carcinoma in obese individuals. Digestive and Liver Disease 2012, 44:1037-1041.
16. Valenti L., Colombo M., Fargion S. PNPLA3 genotype and hepatocellular carcinoma in chronic hepatitis C. Hepatology 2011, 53:1777.
17. Valenti L., Rumi M., Galmozzi E., et al. Patatin-Like phospholipase domain-containing 3 I148M polymorphism, steatosis, and liver damage in chronic hepatitis C. Hepatology 2011, 53:791-799.
18. Gotoda T., Yamada N., Kawamura M., et al. Heterogeneous mutations in the human lipoprotein lipase gene in patients with familial lipoprotein lipase deficiency. Journal of Clinical Investigation 1991, 88:1856-1864.
19. Emi M., Wilson D.E., Iverius P.H., et al. Missense mutation (Gly-Glu188) of human lipoprotein lipase imparting functional deficiency. Journal of Biological Chemistry 1990, 265:5910-5916.
20. Venter J.C., Adams M.D., Myers E.W., et al. The sequence of the human genome. Science 2001, 291:1304-1351.
21. Reich D.E., Lander E.S. On the allelic spectrum of human disease. Trends in Genetics 2001, 17:502-510.
22. Klein R.J., Zeiss C., Chew E.Y., et al. Complement factor H polymorphism in age-related macular degeneration. Science 2005, 308:385-389.
23. Palmer C.N., Maglio C., Pirazzi C., et al. Paradoxical lower serum triglyceride levels and higher type 2 diabetes mellitus susceptibility in obese individuals with the PNPLA3 148M variant. PLoS ONE 2012, 7:e39362.
24. Kollerits B., Coassin S., Beckmann N.D., et al. Genetic evidence for a role of adiponutrin in the metabolism of apolipoprotein B-containing lipoproteins. Human Molecular Genetics 2009, 18:4669-4676.
25. Tian C., Stokowski R.P., Kershenobich D., et al. Variant in PNPLA3 is associated with alcoholic liver disease. Nature Genetics 2009, 42:21-23.
26. Stickel F., Buch S., Lau K., et al. Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians. Hepatology 2011, 53:86-95.
27. Sookoian S., Pirola C.J. 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.
28. Valenti L., Al-Serri A., Daly A.K., et al. Homozygosity for the PNPLA3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease. Hepatology 2010, 51:1209-1217.
29. Rotman Y., Koh C., Zmuda J.M., 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 2010, 52:894-903.
30. Trepo E., Pradat P., Potthoff A., et al. Impact of PNPLA3 (rs738409 C>G) polymorphism on fibrosis progression and steatosis in chronic hepatitis C. Hepatology 2011, 54:60-69.
31. Valenti L., Maggioni P., Piperno A., et al. PNPLA3 I148M polymorphism, steatosis, and liver damage in hereditary hemochromatosis. World Journal of Gastroenterology 2012, 18:2813-2820.
32. Pillay N., Plagnol V., Tarpey P.S., et al. A common single-nucleotide variant in T is strongly associated with chordoma. Nature Genetics 2012, 44:1185-1187.
33. Ginanni Corradini S., Burza M.A., Molinaro A., et al. Patatin-like phospholipase domain containing 3 sequence variant and hepatocellular carcinoma. Hepatology 2011, 53:1776.
34. Guyot E, Sutton A, Rufat P, et al. PNPLA3 rs738409, hepatocellular carcinoma occurrence and risk model prediction in patients with cirrhosis. Journal of Hepatology, pii: S0168-8278(12)00776-3,. doi:10.1016/j.jhep.2012.09.036.
35. Sjöström L., Narbro K., Sjöström C.D., et al. Effects of bariatric surgery on mortality in Swedish obese subjects. New England Journal of Medicine 2007, 357:741-752.
36. Takeuchi Y., Ikeda F., Moritou Y., et al. The impact of patatin-like phospholipase domain-containing protein 3 polymorphism on hepatocellular carcinoma prognosis. Journal of Gastroenterology 2012.
37. Graff M., North K.E., Franceschini N., et al. PNPLA3 gene-by-visceral adipose tissue volume interaction and the pathogenesis of fatty liver disease: the NHLBI Family Heart Study. International Journal of Obesity (London) 2012.
38. Baulande S., Lasnier F., Lucas M., et al. Adiponutrin, a transmembrane protein corresponding to a novel dietary- and obesity-linked mRNA specifically expressed in the adipose lineage. Journal of Biological Chemistry 2001, 276:33336-33344.
39. Lake A.C., Sun Y., Li J.L., et al. Expression, regulation, and triglyceride hydrolase activity of adiponutrin family members. Journal of Lipid Research 2005, 46:2477-2487.
40. Huang Y., He S., Li J.Z., et al. A feed-forward loop amplifies nutritional regulation of PNPLA3. Proceedings of the National Academy of Sciences of the United States of America 2010, 107:7892-7897.
41. Liu Y.M., Moldes M., Bastard J.P., et al. Adiponutrin: a new gene regulated by energy balance in human adipose tissue. Journal of Clinical Endocrinology and Metabolism 2004, 89:2684-2689.
42. Oliver P., Caimari A., Díaz-Rúa R., et al. Diet-induced obesity affects expression of adiponutrin/PNPLA3 and adipose triglyceride lipase, two members of the same family. International Journal of Obesity (London) 2012, 36:225-232.
43. Huang Y., Cohen J.C., Hobbs H.H. Expression and characterization of a PNPLA3 protein isoform (I148M) associated with nonalcoholic fatty liver disease. Journal of Biological Chemistry 2011, 286:37085-37093.
44. Jenkins C.M., Mancuso D.J., Yan W., et al. Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities. Journal of Biological Chemistry 2004, 279:48968-48975.
45. He S., McPhaul C., Li J.Z., et al. A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis. Journal of Biological Chemistry 2010, 285:6706-6715.
46. Kumari M., Schoiswohl G., Chitraju C., et al. Adiponutrin functions as a nutritionally regulated lysophosphatidic acid acyltransferase. Cell Metabolism 2012, 15:691-702.
47. He S., McPhaul C., Li J.Z., et al. A sequence variation (I148M) in PNPlA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis. Journal of Biological Chemistry 2009, 285:6706-6715.
48. Basantani M.K., Sitnick M.T., Cai L., et al. Pnpla3/adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome. Journal of Lipid Research 2011, 52:318-329.
49. Chen W., Chang B., Li L., et al. Patatin-like phospholipase domain-containing 3/adiponutrin deficiency in mice is not associated with fatty liver disease. Hepatology 2010, 52:1134-1142.
50. Pirazzi C., Adiels M., Burza M.A., et al. Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) affects hepatic VLDL secretion in humans and in vitro. Journal of Hepatology 2012.
51. Sevastianova K., Santos A., Kotronen A., et al. Effect of short-term carbohydrate overfeeding and long-term weight loss on liver fat in overweight humans. American Journal of Clinical Nutrition 2012, 96:727-734.
52. Li J.Z., Huang Y., Karaman R., et al. Chronic overexpression of PNPLA3I148M in mouse liver causes hepatic steatosis. Journal of Clinical Investigation 2012.
53. Johansson L.E., Lindblad U., Larsson C.A., et al. Polymorphisms in the adiponutrin gene are associated with increased insulin secretion and obesity. European Journal of Endocrinology/European Federation of Endocrine Societies 2008, 159:577-583.
54. Kotronen A., Johansson L.E., Johansson L.M., et al. A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans. Diabetologia 2009, 52:1056-1060.
55. Kotronen A., Peltonen M., Hakkarainen A., et al. Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors. Gastroenterology 2009, 137:865-872.
56. Sookoian S., Castano G.O., Burgueno A.L., et al. A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity. Journal of Lipid Research 2009, 50:2111-2116.
57. Kantartzis K., Peter A., Machicao F., et al. Dissociation between fatty liver and insulin resistance in humans carrying a variant of the patatin-like phospholipase 3 gene. Diabetes 2009, 58:2616-2623.
58. Romeo S., Sentinelli F., Dash S., et al. Morbid obesity exposes the association between PNPLA3 I148M (rs738409) and indices of hepatic injury in individuals of European descent. International Journal of Obesity (London) 2010, 34:190-194.
59. Speliotes E.K., Butler J.L., Palmer C.D., et al. PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease. Hepatology 2010, 52:904-912.
60. Valenti L., Al-Serri A., Daly A.K., 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.
61. Valenti L., Alisi A., Nobili V. I148M PNPLA3 variant and progressive liver disease: a new paradigm in hepatology. Hepatology 2012.
62. Valenti L., Alisi A., Galmozzi E., et al. I148M patatin-like phospholipase domain-containing 3 gene variant and severity of pediatric nonalcoholic fatty liver disease. Hepatology 2010, 52:1274-1280.
63. Pare G., Ridker P.M., Rose L., et al. Genome-wide association analysis of soluble ICAM-1 concentration reveals novel associations at the NFKBIK, PNPLA3, RELA, and SH2B3 loci. PLoS Genetics 2011, 7:e1001374.
64. Valenti L., Rametta R., Ruscica M., et al. The i148m Pnpla3 polymorphism influences serum adiponectin in patients with fatty liver and healthy controls. BMC Gastroenterology 2012, 12:111.
65. Kadowaki T., Yamauchi T. Adiponectin and adiponectin receptors. Endocrine Reviews 2005, 26:439-451.
66. Stickel F., Hellerbrand C. Non-alcoholic fatty liver disease as a risk factor for hepatocellular carcinoma: mechanisms and implications. Gut 2010, 59:1303-1307.
67. Park E.J., Lee J.H., Yu G.Y., et al. Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell 2010, 140:197-208.
68. Marra F., Bertolani C. Adipokines in liver diseases. Hepatology 2009, 50:957-969.
69. Menendez J.A., Lupu R. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nature Reviews Cancer 2007, 7:763-777.
70. Yamashita T., Honda M., Takatori H., et al. Activation of lipogenic pathway correlates with cell proliferation and poor prognosis in hepatocellular carcinoma. Journal of Hepatology 2009, 50:100-110.
71. Vinciguerra M., Carrozzino F., Peyrou M., et al. Unsaturated fatty acids promote hepatoma proliferation and progression through downregulation of the tumor suppressor PTEN. Journal of Hepatology 2009, 50:1132-1141.
72. Nahon P., Sutton A., Pessayre D., et al. Do genetic variations in antioxidant enzymes influence the course of hereditary hemochromatosis?. Antioxidants and Redox Signalling 2011, 15:31-38.
73. Valenti L., Motta B.M., Soardo G., et al. I148M PNPLA3 polymorphism is associated with clinical features in patients with hepatocellular carcinoma. Journal of Hepatology 2012, 56:S129.