Role of TM6SF2 rs58542926 in the pathogenesis of nonalcoholic pediatric fatty liver disease: A multiethnic study

Hepatology

Volumn 63, Issue 1, 2016, Pages 117-125

  Goffredo, Martina ^a,b   Caprio, Sonia ^a   Feldstein, Ariel E ^c   D'Adamo, Ebe ^d   Shaw, Melissa M ^a   Pierpont, Bridget ^a   Savoye, Mary ^a   Zhao, Hongyu ^a,e   Bale, Allen E ^a   Santoro, Nicola ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF MILANO BICOCCA   (Italy)

^c UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^d CREMONA HOSPITAL   (Italy)

^e YALE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; LOW DENSITY LIPOPROTEIN; LIPOPROTEIN; MEMBRANE PROTEIN; TM6SF2 PROTEIN, HUMAN;

ADOLESCENT; AFRICAN AMERICAN; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALLELISM; ARTICLE; CAUCASIAN; DISEASE ACTIVITY SCORE; DISEASE SEVERITY; FEMALE; HISPANIC; HUMAN; LIPID ANALYSIS; LIVER BIOPSY; LIVER FIBROSIS; MAJOR CLINICAL STUDY; MALE; MARKER GENE; NONALCOHOLIC FATTY LIVER; NUCLEAR MAGNETIC RESONANCE IMAGING; NUCLEAR MAGNETIC RESONANCE SCANNER; ORAL GLUCOSE TOLERANCE TEST; PATHOGENESIS; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM; TRANSMEMBRANE 6 SUPERFAMILY MEMBER 2 GENE; BLOOD; CHILD; COMPARATIVE STUDY; COMPLICATION; GENETICS; OBESITY;

ADOLESCENT; AFRICAN AMERICANS; CHILD; EUROPEAN CONTINENTAL ANCESTRY GROUP; FEMALE; HISPANIC AMERICANS; HUMANS; LIPOPROTEINS; MALE; MEMBRANE PROTEINS; NON-ALCOHOLIC FATTY LIVER DISEASE; OBESITY; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 84952637318     PISSN: 02709139     EISSN: 15273350     Source Type: Journal    
DOI: 10.1002/hep.28283     Document Type: Article

References (23)

1. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002;346:1221-1231.
2. Kozlitina J, Smagris E, Stender S, Nordestgaard BG, Zhou HH, Tybjaerg-Hansen A, et al. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2014;46:352-356.
3. Grandone A, Cozzolino D, Marzuillo P, Cirillo G, Di Sessa A, Ruggiero L, et al. TM6SF2 Glu167Lys polymorphism is associated with low levels of LDL-cholesterol and increased liver injury in obese children. Pediatr Obes 2015; doi:10.1111/ijpo.12032.
4. Liu YL, Reeves HL, Burt AD, Tiniakos D, McPherson S, Leathart JB, et al. TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease. Nat Commun 2014;5:4309.
5. Dongiovanni P, Petta S, Maglio C, Fracanzani AL, Pipitone R, Mozzi E, et al. Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology 2015;61:506-514.
6. 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.
7. 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.
8. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2003;26(Suppl. 1):S5-S20.
9. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999;22:1462-1470.
10. Cali AM, De Oliveira AM, Kim H, Chen S, Reyes-Mugica M, Escalera S, et al. Glucose dysregulation and hepatic steatosis in obese adolescents: is there a link? Hepatology 2009;49:1896-1903.
11. Fishbein MH, Gardner KG, Potter CJ, Schmalbrock P, Smith MA. Introduction of fast MR imaging in the assessment of hepatic steatosis. Magn Reson Imaging 1997;15:287-293.
12. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41:1313-1321.
13. 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.
14. 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.
15. 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.
16. 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.
17. Mahdessian H, Taxiarchis A, Popov S, Silveira A, Franco-Cereceda A, Hamsten A, et al. TM6SF2 is a regulator of liver fat metabolism influencing triglyceride secretion and hepatic lipid droplet content. Proc Natl Acad Sci USA 2014;111:8913-8918.
18. Roh YS, Loomba R, Seki E. The TM6SF2 variants, novel genetic predictors for nonalcoholic steatohepatitis. Gastroenterology 2015;148:252-254.
19. Surakka I, Horikoshi M, Magi R, Sarin AP, Mahajan A, Lagou V, et al. The impact of low-frequency and rare variants on lipid levels. Nat Genet 2015;47:589-597.
20. Rizzo M, Berneis K. Small, dense low-density-lipoproteins and the metabolic syndrome. Diabetes Metab Res Rev 2007;23:14-20.
21. Nielsen SR, Sumner AE, Miller BV 3rd, Turkova H, Klein S, Jensen MD. Free fatty acid flux in African-American and Caucasian adults-effect of sex and race. Obesity (Silver Spring) 2013;21:1836-1842.
22. Holmen OL, Zhang H, Fan Y, Hovelson DH, Schmidt EM, Zhou W, et al. Systematic evaluation of coding variation identifies a candidate causal variant in TM6SF2 influencing total cholesterol and myocardial infarction risk. Nat Genet 2014;46:345-351.
23. Dongiovanni P, Petta S, Mannisto V, Margherita Mancina R, Pipitone R, Karja V, et al. Statin use and nonalcoholic steatohepatitis in at risk individuals. J Hepatol 2015;63:705-712.