Unraveling the genetics of fatty liver in obese children: Additive effect of P446L GCKR and I148M PNPLA3 polymorphisms

Hepatology

Volumn 55, Issue 3, 2012, Pages 661-663

  Valenti, Luca ^a   Alisi, Anna ^b   Nobili, Valerio ^b  

^a UNIVERSITY OF MILAN   (Italy)

^b BAMBINO GESÙ CHILDREN S HOSPITAL   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

GLUCOKINASE REGULATORY PROTEIN; PATATIN LIKE PHOSPHOLIPASE DOMAIN CONTAINING PROTEIN 3; PROTEIN; REGULATOR PROTEIN; UNCLASSIFIED DRUG;

DISEASE COURSE; EDITORIAL; FATTY ACID OXIDATION; GENETIC ASSOCIATION; GENETICS; GENOTYPE; HUMAN; INSULIN RESISTANCE; LIPOGENESIS; LIVER FIBROSIS; NONALCOHOLIC FATTY LIVER; OBESITY; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; FATTY LIVER; FEMALE; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MALE; OBESITY; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 84857429794     PISSN: 02709139     EISSN: 15273350     Source Type: Journal    
DOI: 10.1002/hep.25617     Document Type: Editorial

References (20)

1. Barshop NJ, Sirlin CB, Schwimmer JB, Lavine JE. Review article: epidemiology, pathogenesis and potential treatments of paediatric non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2008; 28: 13-24.
2. Alisi A, Manco M, Panera N, Nobili V. Association between type two diabetes and non-alcoholic fatty liver disease in youth. Ann Hepatol 2009; 8 Suppl. 1: S44-S50.
3. Manco M, Marcellini M, Devito R, Comparcola D, Sartorelli MR, Nobili V. Metabolic syndrome and liver histology in paediatric non-alcoholic steatohepatitis. Int J Obes (Lond) 2008; 32: 381-387.
4. Schwimmer JB, Celedon MA, Lavine JE, Salem R, Campbell N, Schork NJ, et al. Heritability of nonalcoholic fatty liver disease. Gastroenterology 2009; 136: 1585-1592.
5. Guerrero R, Vega GL, Grundy SM, Browning JD. Ethnic differences in hepatic steatosis: an insulin resistance paradox? HEPATOLOGY 2009; 49: 791-801.
6. Makkonen J, Pietilainen KH, Rissanen A, Kaprio J, Yki-Jarvinen H. Genetic factors contribute to variation in serum alanine aminotransferase activity independent of obesity and alcohol: a study in monozygotic and dizygotic twins. J Hepatol 2009; 50: 1035-1042.
7. Valenti L, Alisi A, Galmozzi E, Bartuli A, Del Menico B, Alterio A, et al. I148M patatin-like phospholipase domain-containing 3 gene variant and severity of pediatric nonalcoholic fatty liver disease. HEPATOLOGY 2010; 52: 1274-1280.
8. 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.
9. Valenti L, Al-Serri A, Daly AK, Galmozzi E, Rametta R, Dongiovanni P, et al. Homozygosity for the PNPLA3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease. HEPATOLOGY 2010; 51: 1209-1217.
10. 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.
11. Valenti L, Alisi A, Nobili V. I148M PNPLA3 variant and progressive liver disease: a new paradigm in hepatology. HEPATOLOGY 2012; doi:10.1002/hep.25506.
12. Speliotes EK, Yerges-Armstrong LM, Wu J, Hernaez R, Kim LJ, Palmer CD, et al. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet 2011; 7: e1001324.
13. Petersen KF, Dufour S, Hariri A, Nelson-Williams C, Foo JN, Zhang XM, et al. Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease. N Engl J Med 2010; 362: 1082-1089.
14. Santoro N, Zhang CK, Zhao H, Pakstis AJ, Kim G, Kursawe R, 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.
15. Santoro N, Kursawe R, D'Adamo E, Dykas DJ, Zhang CK, Bale AE, 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 2010; 52: 1189-1182.
16. Kozlitina J, Boerwinkle E, Cohen JC, Hobbs HH. Dissociation between APOC3 variants, hepatic triglyceride content and insulin resistance. HEPATOLOGY 2011; 53: 467-474.
17. Valenti L, Nobili V, Al-Serri A, Rametta R, Leathart JB, Zappa MA, 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.
18. Beer NL, Tribble ND, McCulloch LJ, Roos C, Johnson PR, Orho-Melander M, 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 2009; 18: 4081-4088.
19. Dongiovanni P, Valenti L, Rametta R, Daly AK, Nobili V, Mozzi E, et al. Genetic variants regulating insulin receptor signaling are associated with the severity of liver damage in patients with nonalcoholic fatty liver disease. Gut 2010; 59: 267-273.
20. Valenti L, Motta BM, Alisi A, Sartorelli R, Bonaiuto G, Dongiovanni P, et al. LPIN1 rs13412852 polymorphism in pediatric non-alcoholic fatty liver disease. J Pediatr Gastroenterol Nutr 2012; doi:10.1097/MPG.0b013e3182442a55.