The UCP2 -866 G>A promoter region polymorphism is associated with nonalcoholic steatohepatitis.

Liver International

Volumn 35, Issue 5, 2015, Pages 1574-1580

  Fares, Roberta ^a   Petta, Salvatore ^b   Lombardi, Rosa ^a   Grimaudo, Stefania ^b   Dongiovanni, Paola ^a   Pipitone, Rosaria ^b   Rametta, Raffaela ^a   Fracanzani, Anna Ludovica ^a   Mozzi, Enrico ^a   Craxì, Antonio ^b   Fargion, Silvia ^a   Sesti, Giorgio ^c   Valenti, Luca ^a  

^a UNIVERSITY OF MILAN   (Italy)

^b UNIVERSITY OF PALERMO   (Italy)

^c UNIVERSITY MAGNA GRAECIA OF CATANZARO   (Italy)

Author keywords

Genetic polymorphism; Lipid metabolism; Liver; Mitochondria; Nonalcoholic steatohepatitis; Uncoupling protein 2

Indexed keywords

CHOLESTEROL; GLIBENCLAMIDE; MESSENGER RNA; UNCOUPLING PROTEIN 2; ION CHANNEL; MITOCHONDRIAL PROTEIN; MITOCHONDRIAL UNCOUPLING PROTEIN 2;

ADULT; AGE; ALLELE; ARTICLE; CHOLESTEROL BLOOD LEVEL; COHORT ANALYSIS; CONTROLLED STUDY; DNA POLYMORPHISM; FEMALE; GENDER; GENE EXPRESSION; GENETIC ASSOCIATION; GENETIC PREDISPOSITION; GENETIC RISK; GENOTYPE; HUMAN; HUMAN TISSUE; HYPERGLYCEMIA; IMPAIRED GLUCOSE TOLERANCE; ITALIAN (CITIZEN); LIVER BIOPSY; LIVER FIBROSIS; LIVER INJURY; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; NONALCOHOLIC FATTY LIVER; OLIGONUCLEOTIDE PROBE; PROMOTER REGION; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; STEATOSIS; TISSUE SECTION; AGED; CASE CONTROL STUDY; CLINICAL TRIAL; GENETIC POLYMORPHISM; GENETICS; INSULIN RESISTANCE; LIPID METABOLISM; LIVER; MULTICENTER STUDY; PATHOLOGY; RISK FACTOR; STATISTICAL MODEL;

ADULT; AGED; ALLELES; CASE-CONTROL STUDIES; FEMALE; GENE EXPRESSION; GENOTYPE; HUMANS; INSULIN RESISTANCE; ION CHANNELS; LIPID METABOLISM; LIVER; LOGISTIC MODELS; MALE; MIDDLE AGED; MITOCHONDRIAL PROTEINS; NON-ALCOHOLIC FATTY LIVER DISEASE; POLYMORPHISM, GENETIC; PROMOTER REGIONS, GENETIC; RISK FACTORS;

EID: 84927589804     PISSN: 14783223     EISSN: 14783231     Source Type: Journal    
DOI: 10.1111/liv.12707     Document Type: Article

References (41)

1. Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004; 40: 1387-95.
2. Bellentani S, Saccoccio G, Masutti F, et al. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med 2000; 132: 112-7.
3. Marchesini G, Brizi M, Bianchi G, et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 2001; 50: 1844-50.
4. Musso G, Gambino R, Cassader M, Pagano G. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med 2012; 43: 617-49.
5. Fabbrini E, Mohammed BS, Magkos F, et al. Alterations in adipose tissue and hepatic lipid kinetics in obese men and women with nonalcoholic fatty liver disease. Gastroenterology 2008; 134: 424-31.
6. Caldwell SH, Swerdlow RH, Khan EM, et al. Mitochondrial abnormalities in non-alcoholic steatohepatitis. J Hepatol 1999; 31: 430-4.
7. Day CP. From fat to inflammation. Gastroenterology 2006; 130: 207-10.
8. Sunny NE, Parks EJ, Browning JD, Burgess SC. Excessive hepatic mitochondrial TCA cycle and gluconeogenesis in humans with nonalcoholic fatty liver disease. Cell Metab 2011; 14: 804-10.
9. Perez-Carreras M, del Hoyo P, Martin MA, et al. Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis. Hepatology 2003; 38: 999-1007.
10. Serviddio G, Sastre J, Bellanti F, et al. Mitochondrial involvement in non-alcoholic steatohepatitis. Mol Aspects Med 2008; 29: 22-35.
11. Dongiovanni P, Anstee QM, Valenti L. Genetic predisposition in NAFLD and NASH: impact on severity of liver disease and response to treatment. Curr Pharm Des 2013; 19: 5219-38.
12. Romeo S, Kozlitina J, Xing C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008; 40: 1461-5.
13. Valenti L, Al-Serri A, Daly AK, et al. Homozygosity for the PNPLA3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease. Hepatology 2010; 51: 1209-17.
14. Videla LA, Rodrigo R, Orellana M, et al. Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients. Clin Sci 2004; 106: 261-8.
15. Al-Serri A, Anstee QM, Valenti L, et al. The SOD2 C47T polymorphism influences NAFLD fibrosis severity: evidence from case-control and intra-familial allele association studies. J Hepatol 2011; 56: 448-54.
16. Serviddio G, Bellanti F, Tamborra R, et al. Uncoupling protein-2 (UCP2) induces mitochondrial proton leak and increases susceptibility of non-alcoholic steatohepatitis (NASH) liver to ischaemia-reperfusion injury. Gut 2008; 57: 957-65.
17. Sesti G, Cardellini M, Marini MA, et al. A common polymorphism in the promoter of UCP2 contributes to the variation in insulin secretion in glucose-tolerant subjects. Diabetes 2003; 52: 1280-3.
18. D'adamo M, Perego L, Cardellini M, et al. The -866A/A genotype in the promoter of the human uncoupling protein 2 gene is associated with insulin resistance and increased risk of type 2 diabetes. Diabetes 2004; 53: 1905-10.
19. Bulotta A, Ludovico O, Coco A, et al. The common -866G/A polymorphism in the promoter region of the UCP-2 gene is associated with reduced risk of type 2 diabetes in Caucasians from Italy. J Clin Endocrinol Metab 2005; 90: 1176-80.
20. Jia JJ, Zhang X, Ge CR, Jois M. The polymorphisms of UCP2 and UCP3 genes associated with fat metabolism, obesity and diabetes. Obes Rev 2009; 10: 519-26.
21. Mathurin P, Hollebecque A, Arnalsteen L, et al. Prospective study of the long-term effects of bariatric surgery on liver injury in patients without advanced disease. Gastroenterology 2009; 137: 532-40.
22. Rametta R, Mozzi E, Dongiovanni P, et al. Increased insulin receptor substrate 2 expression is associated with steatohepatitis and altered lipid metabolism in obese subjects. Int J Obes (Lond) 2013; 37: 986-92.
23. Bedogni G, Bellentani S, Miglioli L, et al. The fatty liver index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol 2006; 6: 33.
24. Valenti L, Rametta R, Ruscica M, et al. The i148 m Pnpla3 polymorphism influences serum adiponectin in patients with fatty liver and healthy controls. BMC Gastroenterol 2012; 12: 111.
25. Kleiner DE, Brunt EM, van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41: 1313-21.
26. Dongiovanni P, Donati B, Fares R, et al. PNPLA3 I148M polymorphism and progressive liver disease. World J Gastroenterol 2013; 19: 6969-78.
27. 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: 1883-94.
28. Skulachev VP. Fatty acid circuit as a physiological mechanism of uncoupling of oxidative phosphorylation. FEBS Lett 1991; 294: 158-62.
29. Schrauwen P, Hesselink MK. The role of uncoupling protein 3 in fatty acid metabolism: protection against lipotoxicity? Proc Nutr Soc 2004; 63: 287-92.
30. Azzu V, Brand MD. The on-off switches of the mitochondrial uncoupling proteins. Trends Biochem Sci 2010; 35: 298-307.
31. Baffy G, Zhang CY, Glickman JN, Lowell BB. Obesity-related fatty liver is unchanged in mice deficient for mitochondrial uncoupling protein 2. Hepatology 2002; 35: 753-61.
32. Brand MD, Esteves TC. Physiological functions of the mitochondrial uncoupling proteins UCP2 and UCP3. Cell Metab 2005; 2: 85-93.
33. Videla LA, Rodrigo R, Araya J, Poniachik J. Oxidative stress and depletion of hepatic long-chain polyunsaturated fatty acids may contribute to nonalcoholic fatty liver disease. Free Radic Biol Med 2004; 37: 1499-507.
34. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001; 414: 813-20.
35. Paradis V, Perlemuter G, Bonvoust F, et al. High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: a potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis. Hepatology 2001; 34(4 Pt 1): 738-44.
36. Berardi MJ, Chou JJ. Fatty acid flippase activity of UCP2 is essential for its proton transport in mitochondria. Cell Metab 2014; 20: 541-52.
37. 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: 352-6.
38. Dongiovanni P, Petta S, Maglio C, et al. TM6SF2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology 2015; doi: 10.1002/hep.27490, PMID: 25251399.
39. Pallottini V, Montanari L, Cavallini G, et al. Mechanisms underlying the impaired regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in aged rat liver. Mech Ageing Dev 2004; 125: 633-9.
40. Min HK, Kapoor A, Fuchs M, et al. Increased hepatic synthesis and dysregulation of cholesterol metabolism is associated with the severity of nonalcoholic fatty liver disease. Cell Metab 2012; 15: 665-74.
41. Qian L, Xu K, Xu X, et al. UCP2 -866G/A, Ala55Val and UCP3 -55C/T polymorphisms in association with obesity susceptibility - a meta-analysis study. PLoS ONE 2013; 8: e58939.