TM6SF2 Glu167Lys polymorphism is associated with low levels of LDL-cholesterol and increased liver injury in obese children

Pediatric Obesity

Volumn 11, Issue 2, 2016, Pages 115-119

  Grandone, A ^a   Cozzolino, D ^b   Marzuillo, P ^a   Cirillo, G ^a   Di Sessa, A ^a   Ruggiero, L ^a   Di Palma, M R ^a   Perrone, L ^a   Miraglia Del Giudice, E ^a  

^a Department of Woman   (Italy)

^b SECOND UNIVERSITY OF NAPLES   (Italy)

Author keywords

NAFLD; non HDL C; PNPLA3; TMS6SF2

Indexed keywords

ASPARTATE AMINOTRANSFERASE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PATATIN LIKE PHOSPHOLIPASE 3; PHOSPHOLIPASE; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; ALANINE AMINOTRANSFERASE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LIPOPROTEIN; LIPOPROTEIN TRIGLYCERIDE; MEMBRANE PROTEIN; TM6SF2 PROTEIN, HUMAN; TRIACYLGLYCEROL LIPASE;

ADOLESCENT; ADOLESCENT OBESITY; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALLELE; ARTICLE; CARDIOVASCULAR RISK; CHILD; CHILDHOOD OBESITY; CHOLESTEROL BLOOD LEVEL; ECHOGRAPHY; FEMALE; GENE; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENETIC PREDISPOSITION; GENETIC VARIABILITY; GENOTYPE; HEPATOGRAPHY; HOMOZYGOTE; HUMAN; HYPERTRANSAMINASEMIA; LIVER INJURY; MAJOR CLINICAL STUDY; MALE; NONALCOHOLIC FATTY LIVER; PNPLA3 GENE; PRIORITY JOURNAL; TM6SF2 GENE; TRIACYLGLYCEROL BLOOD LEVEL; BLOOD; COMPLICATION; ENZYMOLOGY; EPIDEMIOLOGY; GENETICS; ITALY; LIVER; METABOLISM; NON-ALCOHOLIC FATTY LIVER DISEASE; RISK FACTOR; SINGLE NUCLEOTIDE POLYMORPHISM;

ADOLESCENT; ALANINE TRANSAMINASE; ALLELES; CHILD; CHOLESTEROL, HDL; CHOLESTEROL, LDL; FEMALE; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HUMANS; ITALY; LIPASE; LIPOPROTEINS; LIVER; MALE; MEMBRANE PROTEINS; NON-ALCOHOLIC FATTY LIVER DISEASE; PEDIATRIC OBESITY; POLYMORPHISM, SINGLE NUCLEOTIDE; RISK FACTORS; TRIGLYCERIDES;

EID: 84960461431     PISSN: 20476302     EISSN: 20476310     Source Type: Journal    
DOI: 10.1111/ijpo.12032     Document Type: Article

References (30)

1. Younossi ZM, Stepanova M, Rafiq N, et al. Pathologic criteria for nonalcoholic steatohepatitis: interprotocol agreement and ability to predict liver-related mortality. Hepatology 2011; 53: 1874-1882.
2. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ,. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 1999; 116: 1413-1419.
3. Nobili V, Alisi A, Grimaldi C, et al. Non-alcoholic fatty liver disease and hepatocellular carcinoma in a 7-year-old obese boy: coincidence or comorbidity? Pediatr Obes 2014; 9: 99-102.
4. Aly FZ, Kleiner DE,. Update on fatty liver disease and steatohepatitis. Adv Anat Pathol 2011; 18: 294-300.
5. Welsh JA, Karpen S, Vos MB,. Increasing prevalence of nonalcoholic fatty liver disease among United States adolescents, 1988-1994 to 2007-2010. J Pediatr 2013; 162: 496-500.
6. Marzuillo P, Miraglia del Giudice E, Santoro N,. Pediatric non-alcoholic fatty liver disease: new insights and future directions. World J Hepatol 2014; 6: 217-225.
7. Marzuillo P, Miraglia del Giudice E, Santoro N,. Pediatric fatty liver disease: role of ethnicity and genetics. World J Gastroenterol 2014; 20: 7347-7355.
8. Romeo S, Kozlitina J, Xing C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008; 40: 1461-1465.
9. Miraglia del Giudice E, Grandone A, Cirillo G, et al. The association of PNPLA3 variants with liver enzymes in childhood obesity is driven by the interaction with abdominal fat. PLoS ONE 2011; 6: e27933.
10. Marzuillo P, Grandone A, Perrone L, Miraglia del Giudice E,. Weight loss allows the dissection of the interaction between abdominal fat and PNPLA3 (adiponutrin) in the liver damage of obese children. J Hepatol 2013; 59: 1143-1144.
11. Kozlitina J, Smagris E, Stender S, et al. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2014; 46: 352-356.
12. Holmen OL, Zhang H, Fan Y, 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.
13. Dongiovanni P, Petta S, Maglio C, et al. TM6SF2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology 2015; 61: 506-514.
14. Cacciari E, Milani S, Balsamo A, et al. Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr). J Endocrinol Invest 2006; 29: 581-593.
15. Santoro N, Miraglia del Giudice E, Grandone A, et al. Y2 receptor gene variants reduce the risk of hypertension in obese children and adolescents. J Hypertens 2008; 26: 1590-1594.
16. Santoro N, Amato A, Grandone A, et al. Predicting metabolic syndrome in obese children and adolescents: look, measure and ask. Obes Facts 2013; 6: 48-56.
17. Cole TJ,. The LMS method for constructing normalized growth standards. Eur J Clin Nutr 1990; 44: 45-60.
18. Tanner JM, Whitehouse RH,. Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child 1976; 51: 170-179.
19. Marzuillo P, Grandone A, Conte M, et al. Novel association between a non-synonymous variant (R270H) of the G-protein-coupled receptor 120 and liver injury in obese children and adolescents. J Pediatr Gastroenterol Nutr 2014; 59: 472-475.
20. 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.
21. Sullivan JS, Le MT, Pan Z, et al. Oral fructose absorption in obese children with non-alcoholic fatty liver disease. Pediatr Obes 2014 [Epub ahead of print]. DOI: 10.1111/ijpo.238.
22. Goran MI, Walker R, Le KA, et al. Effects of PNPLA3 on liver fat and metabolic profile in Hispanic children and adolescents. Diabetes 2010; 59: 3127-3130.
23. Davis JN, Lê KA, Walker RW, et al. Increased hepatic fat in overweight Hispanic youth influenced by interaction between genetic variation in PNPLA3 and high dietary carbohydrate and sugar consumption. Am J Clin Nutr 2010; 92: 1522-1527.
24. Santoro N, Savoye M, Kim G, et al. Hepatic fat accumulation is modulated by the interaction between the rs738409 variant in the PNPLA3 gene and the dietary omega6/omega3 PUFA intake. PLoS ONE 2012; 7: e37827.
25. Mahdessian H, Taxiarchis A, Popov S, et al. TM6SF2 is a regulator of liver fat metabolism influencing triglyceride secretion and hepatic lipid droplet content. Proc Natl Acad Sci U S A 2014; 111: 8913-8918.
26. Wong VW, Wong GL, Tse CH, Chan HL,. Prevalence of TM6SF2 variant and nonalcoholic fatty liver disease in Chinese. J Hepatol 2014; 61: 708-709.
27. Liu YL, Reeves HL, Burt AD, et al. TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease. Nat Commun 2014; 5: 4309.
28. Miller M, Ginsberg HN, Schaefer EJ,. Relative atherogenicity and predictive value of non-high-density lipoprotein cholesterol for coronary heart disease. Am J Cardiol 2008; 101: 1003-1008.
29. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002; 106: 3143-3421.
30. Frontini MG, Srinivasan SR, Xu J, Tang R, Bond MG, Berenson GS,. Usefulness of childhood non-high density lipoprotein cholesterol levels versus other lipoprotein measures in predicting adult subclinical atherosclerosis: the Bogalusa Heart Study. Pediatrics 2008; 121: 924-929.