Variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver in obese children and adolescents

Hepatology

Volumn 55, Issue 3, 2012, Pages 781-789

  Santoro, Nicola ^a   Zhang, Clarence K ^a   Zhao, Hongyu ^a   Pakstis, Andrew J ^a   Kim, Grace ^a   Kursawe, Romy ^a   Dykas, Daniel J ^a   Bale, Allen E ^a   Giannini, Cosimo ^a   Pierpont, Bridget ^a   Shaw, Melissa M ^a   Groop, Leif ^b   Caprio, Sonia ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b LUND UNIVERSITY DIABETES CENTRE   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; APOLIPOPROTEIN C3; ASPARTATE AMINOTRANSFERASE; GLUCOKINASE; GLUCOKINASE REGULATORY PROTEIN; GLUCOSE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; INSULIN; LIPOPROTEIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; REGULATOR PROTEIN; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; VERY LOW DENSITY LIPOPROTEIN;

ADOLESCENT; ADOLESCENT DISEASE; AFRICAN AMERICAN; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BODY MASS; CAUCASIAN; CHILD; CHILDHOOD DISEASE; CHOLESTEROL BLOOD LEVEL; DISEASE ASSOCIATION; DISEASE PREDISPOSITION; FAT CONTENT; FATTY LIVER; FEMALE; GENE FREQUENCY; GENETIC VARIABILITY; GENOTYPE; GLUCOSE BLOOD LEVEL; HAPLOTYPE; HISPANIC; HUMAN; HYPERTRIGLYCERIDEMIA; INSULIN BLOOD LEVEL; INSULIN SENSITIVITY; LIPID STORAGE; MAJOR CLINICAL STUDY; MALE; OBESITY; ORAL GLUCOSE TOLERANCE TEST; PARTICLE SIZE; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; SCHOOL CHILD; SINGLE NUCLEOTIDE POLYMORPHISM; TRIACYLGLYCEROL BLOOD LEVEL;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ADOLESCENT; AFRICAN AMERICANS; APOLIPOPROTEIN C-III; CHILD; EUROPEAN CONTINENTAL ANCESTRY GROUP; FATTY LIVER; FEMALE; GENE FREQUENCY; GENETIC PREDISPOSITION TO DISEASE; HAPLOTYPES; HISPANIC AMERICANS; HUMANS; LIPASE; LIPOPROTEINS, VLDL; MALE; MEMBRANE PROTEINS; OBESITY; POLYMORPHISM, SINGLE NUCLEOTIDE; RISK FACTORS; TRIGLYCERIDES;

EID: 84857398069     PISSN: 02709139     EISSN: 15273350     Source Type: Journal    
DOI: 10.1002/hep.24806     Document Type: Article

References (34)

1. Mencin AA, Lavine JE. Nonalcoholic fatty liver disease in children. Curr Opin Clin Nutr Metab Care 2011; 14: 151-157.
2. Feldstein AE, Charatcharoenwitthaya P, Treeprasertsuk S, Benson JT, Enders FB, Angulo P. The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years. Gut 2009; 58: 1538-1544.
3. 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.
4. Romeo S, Huang-Doran I, Baroni MG, Kotronen A. Unravelling the pathogenesis of fatty liver disease: patatin-like phospholipase domain-containing 3 protein. Curr Opin Lipidol 2010; 21: 247-252.
5. 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: 1281-1290.
6. 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.
7. 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.
8. Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes of BioMedical Research, Saxena R, Voight BF, Lyssenko V, Burtt NP, de Bakker PI, Chen H, et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 2007; 316: 1331-1336.
9. Willer CJ, Sanna S, Jackson AU, Scuteri A, Bonnycastle LL, Clarke R, et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet 2008; 40: 161-169.
10. Matschinsky FM. Glucokinase as glucose sensor and metabolic signal generator in pancreatic beta-cells and hepatocytes. Diabetes 1990; 39: 647-652.
11. Matschinsky FM. Regulation of pancreatic beta-cell glucokinase: from basics to therapeutics. Diabetes 2002; 51: S394-S404.
12. Slosberg ED, Desai UJ, Fanelli B, St Denny I, Connelly S, Kaleko M, et al. Treatment of type 2 diabetes by adenoviral-mediated overexpression of the glucokinase regulatory protein. Diabetes 2001; 50: 1813-1820.
13. 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.
14. Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 2005; 115: 1343-1351.
15. Speliotes EK, Yerges-Armstrong LM, Wu J, Hernaez R, Kim LJ, Palmer CD, Gudnason V, 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.
16. Dammerman M, Sandkuijl LA, Halaas JL, Chung W, Breslow JL. An apolipoprotein CIII haplotype protective against hypertriglyceridemia is specified by promoter and 3' untranslated region polymorphisms. Proc Natl Acad Sci U S A 1993; 90: 4562-4566.
17. Cook S, Auinger P, Li C, Ford ES. Metabolic syndrome rates in United States adolescents, from the National Health and Nutrition Examination Survey, 1999-2002. J Pediatr 2008; 152: 165-170.
18. Chen W, Chang B, Li L, Chan L. Patatin-like phospholipase domain-containing 3/adiponutrin deficiency in mice is not associated with fatty liver disease. HEPATOLOGY 2010; 52: 1134-1142.
19. He S, McPhaul C, Li JZ, Garuti R, Kinch L, Grishin NV, et al. A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis. J Biol Chem 2010; 285: 6706-6715.
20. Huang Y, He S, Li JZ, Seo YK, Osborne TF, Cohen JC, et al. A feed-forward loop amplifies nutritional regulation of PNPLA3. Proc Natl Acad Sci U S A 2010; 107: 7892-7897.
21. Browning JD, Cohen JC, Hobbs HH. Patatin-like phospholipase domain-containing 3 and the pathogenesis and progression of pediatric nonalcoholic fatty liver disease. HEPATOLOGY 2010; 52: 1189-1192.
22. Huang Y, Cohen JC, Hobbs HH. Expression and characterization of a PNPLA3 isoform (I148M) associated with nonalcoholic fatty liver disease. J Biol Chem 2011; 286: 37085-37093.
23. Varbo A, Benn M, Tybjærg-Hansen A, Grande P, Nordestgaard BG. TRIB1 and GCKR polymorphisms, lipid levels, and risk of ischemic heart disease in the general population. Arterioscler Thromb Vasc Biol 2011; 31: 51-57.
24. Kozian DH, Barthel A, Cousin E, Brunnhöfer R, Anderka O, März W, et al. Glucokinase-activating GCKR polymorphisms increase plasma levels of triglycerides and free fatty acids, but do not elevate cardiovascular risk in the Ludwigshafen Risk and Cardiovascular Health Study. Horm Metab Res 2010; 42: 502-506.
25. Mohás M, Kisfali P, Járomi L, Maász A, Fehér E, Csöngei V, et al. GCKR gene functional variants in type 2 diabetes and metabolic syndrome: do the rare variants associate with increased carotid intima-media thickness? Cardiovasc Diabetol 2010; 9: 79.
26. Rasmussen-Torvik LJ, Li M, Kao WH, Couper D, Boerwinkle E, Bielinski SJ, et al. Association of a fasting glucose genetic risk score with subclinical atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) study. Diabetes 2011; 60: 331-335.
27. D'Adamo E, Cali AM, Weiss R, Santoro N, Pierpont B, Northrup V, et al. Central role of fatty liver in the pathogenesis of insulin resistance in obese adolescents. Diabetes Care 2010; 33: 1817-1822.
28. D'Adamo E, Northrup V, Weiss R, Santoro N, Pierpont B, Savoye M, et al. Ethnic differences in lipoprotein subclasses in obese adolescents: importance of liver and intraabdominal fat accretion. Am J Clin Nutr 2010; 92: 500-508.
29. Schwimmer JB, Pardee PE, Lavine JE, Blumkin AK, Cook S. Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease. Circulation 2008; 118: 277-283.
30. Barker A, Sharp SJ, Timpson NJ, Bouatia-Naji N, Warrington NM, Kanoni S, et al. Association of genetic loci with glucose levels in childhood and adolescence: a meta-analysis of over 6, 000 children. Diabetes 2011; 60: 1805-1812.
31. Kozlitina J, Boerwinkle E, Cohen JC, Hobbs HH. Dissociation between APOC3 variants, hepatic triglyceride content and insulin resistance. HEPATOLOGY 2011; 53: 467-474.
32. 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.
33. Sentinelli F, Romeo S, Maglio C, Incani M, Burza MA, Scano F, 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 2011; 10: 93.
34. Dongiovanni P, Valenti L, Rametta R, Daly AK, Nobili V, Mozzi E, 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 2010; 59: 267-273.