TM6SF2 E167K variant is associated with severe steatosis in chronic hepatitis C, regardless of PNPLA3 polymorphism

Liver International

Volumn 35, Issue 8, 2015, Pages 1959-1963

  Coppola, Nicola ^a   Rosa, Zampino ^a   Cirillo, Grazia ^a   Stanzione, Maria ^a   Macera, Margherita ^a   Boemio, Adriana ^a   Grandone, Anna ^a   Pisaturo, Mariantonietta ^a   Marrone, Aldo ^a   Adinolfi, Luigi E ^a   Sagnelli, Evangelista ^a   Miraglia del Giudice, Emanuele ^a  

^a SECOND UNIVERSITY OF NAPLES   (Italy)

Author keywords

HCV infection; PNPLA3 polymorphism; Steatosis; TM6SF2 polymorphism

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; GAMMA GLUTAMYLTRANSFERASE; ADIPONUTRIN, HUMAN; ANTIVIRUS AGENT; MEMBRANE PROTEIN; TM6SF2 PROTEIN, HUMAN; TRIACYLGLYCEROL LIPASE;

ADULT; ALLELE; ARTICLE; BODY MASS; CHRONIC HEPATITIS C; FATTY LIVER; FEMALE; GENE; HETEROZYGOTE; HOMOZYGOTE; HUMAN; LIVER BIOPSY; LIVER FIBROSIS; LIVER HISTOLOGY; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; NON INSULIN DEPENDENT DIABETES MELLITUS; NONALCOHOLIC FATTY LIVER; PATATIN LIKE PHOSPHOLIPASE DOMAIN CONTAINING 3 GENE; SINGLE NUCLEOTIDE POLYMORPHISM; TRANSMEMBRANE SIX SUPERFAMILY MEMBER 2 GENE; WAIST CIRCUMFERENCE; ANALYSIS OF VARIANCE; CLINICAL TRIAL; COHORT ANALYSIS; COMPLICATION; GENETIC PREDISPOSITION; GENETICS; GENOTYPE; HEPATITIS C, CHRONIC; INCIDENCE; ITALY; MULTICENTER STUDY; NON-ALCOHOLIC FATTY LIVER DISEASE; PROGNOSIS; RETROSPECTIVE STUDY; RISK ASSESSMENT; SEVERITY OF ILLNESS INDEX; STATISTICAL MODEL;

ADULT; ANALYSIS OF VARIANCE; ANTIVIRAL AGENTS; COHORT STUDIES; FEMALE; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HEPATITIS C, CHRONIC; HUMANS; INCIDENCE; ITALY; LINEAR MODELS; LIPASE; MALE; MEMBRANE PROTEINS; MIDDLE AGED; NON-ALCOHOLIC FATTY LIVER DISEASE; POLYMORPHISM, SINGLE NUCLEOTIDE; PROGNOSIS; RETROSPECTIVE STUDIES; RISK ASSESSMENT; SEVERITY OF ILLNESS INDEX;

EID: 84937979132     PISSN: 14783223     EISSN: 14783231     Source Type: Journal    
DOI: 10.1111/liv.12781     Document Type: Article

References (23)

1. Wong JB, McQuillan GM, McHutchison JG, Poynard T. Estimating future hepatitis C morbidity, mortality, and costs in the United States. Am J Public Health 2000; 90: 1562-9.
2. Missiha SB, Ostrowski M, Heathcote EJ. Disease progression in chronic hepatitis C: modifiable and nonmodifiable factors. Gastroenterology 2008; 134: 1699-714.
3. Sagnelli E, Coppola N, Scolastico C, et al. Virological and clinical aspects of reciprocal inhibitory effect of hepatitis B, C, and Delta viruses in patients with chronic hepatitis. Hepatology 2000; 32: 1106-10.
4. Adinolfi LE, Gambardella M, Andreana A, et al. Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. Hepatology 2001; 33: 1358-64.
5. Hutchinson SJ, Bird SM, Goldberg DJ. Influence of alcohol on the progression of hepatitis C virus infection: a meta-analysis. Clin Gastroenterol Hepatol 2005; 3: 1150-9.
6. Sagnelli E, Pisaturo M, Stanzione M, et al. Presentation, outcomes, and response to therapy among patients with acute exacerbation of chronic hepatitis C. Clin Gastroenterol Hepatol 2013; 11: e11.
7. Trépo E, Pradat P, Potthoff A, et al. Impact of Patatin-like Phospholipase-3 (rs738409C>G) polymorphism on fibrosis progression and steatosis in chronic hepatitis C. Hepatology 2011; 54: 60-9.
8. Valenti L, Rumi M, Galmozzi E, et al. Patatin-Like Phospholipase Domain-Containing 3 I148M polymorphism, steatosis, and liver damage in chronic hepatitis C. Hepatology 2011; 53: 791-9.
9. Zampino R, Coppola N, Cirillo G, et al. Abdominal fat interacts with PNPLA3 I148M, but not with the APOC3 variant in the pathogenesis of liver steatosis in chronic hepatitis C. J Vir Hepat 2013; 20: 517-23.
10. 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 USA 2014; 111: 8913-8.
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: 352-6.
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: 345-51.
13. 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.
14. Coppola N, Zampino R, Sagnelli C, et al. Cannabinoid receptor 2-63 QQ variant is associated with persistently normal aminotransferase serum levels in chronic hepatitis C. PLoS ONE 2014; 18: e99450.
15. Ishak K, Baptista A, Bianchi L, et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995; 22: 696-9.
16. 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.
17. Italian Association for the Study of the Liver, Italian Society of Infectious, Tropical Diseases; Italian Society for the Study of Sexually Transmitted Diseases. Practice guidelines for the treatment of hepatitis C: recommendations from an AISF/SIMIT/SIMAST Expert Opinion Meeting. Dig Liver Dis. 2010;42:81-91.
18. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol 2011; 55: 245-64.
19. Soverini V, Persico M, Bugianesi E, et al. HBV and HCV infection in type 2 diabetes mellitus: a survey in three diabetes units in different Italian areas. Acta Diabetol 2011; 48: 337-43.
20. Kathiresan S, Willer CJ, Peloso GM, et al. Common variants at 30 loci contribute to polygenic dyslipidemia. Nat Genet 2009; 41: 56-65.
21. Speliotes EK, Yerges-Armstrong LM, Wu J, 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.
22. Sookoian S, Castaño GO, Scian R, et al. Genetic variation in TM6SF2 and the risk of nonalcoholic fatty liver disease and histological disease severity. Hepatology 2015. In press; doi: 10.1002/hep.27556
23. Dongiovanni P, Petta S, Maglio C, et al. TM6SF2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology 2015. In Press; doi:10.1002/hep.27490.