title: TM6SF2 E167K variant is associated with severe steatosis in chronic hepatitis C, regardless of PNPLA3 polymorphism.
abstract: OBJECTIVE
  A common non-synonymous polymorphism, E167K, in transmembrane six superfamily member 2 (TM6SF2) gene has been recently associated with an increased hepatic triglyceride content, dyslipidemia and liver fibrosis in NAFLD patients. We investigated possible associations between the TM6SF2 variants and liver lesions in chronic hepatitis C.
  
  
  METHODS
  148 consecutive patients with biopsy proven anti-HCV/HCV-RNA-positive chronic hepatitis, naive for antiviral therapy, were genotyped for TM6SF2 E167K and PNPLA3 I148M variants.
  
  
  RESULTS
  The score of liver steatosis was higher in the 18 patients with TM6SF2 E167K variant (mean 1.9 ± 1.3) than in the 130 homozygotes for TM6SF2 167E allele (1.1 ± 1.1, P = 0.02), and the prevalence of a steatosis score ≥ 3 was 33.3% vs. 12.3% respectively (P = 0.02). No difference in necroinflammatory or fibrosis scores was found between the two groups. A general linear model identified as independent predictors of steatosis TM6SF2 E167K and PNPLA3 M148M variants and waist circumference (P = 0.0376, P = 0.0069 and P = 0.0273 respectively).
  
  
  CONCLUSIONS
  This is the first demonstration that TM6SF2 E167K variant is an independent predictor of liver steatosis in chronic hepatitis C.
authors.affiliation: Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Coppola
authors.affiliation: Internal Medicine and Hepatology, Second University of Naples, Naples, Italy.
authors.forename: Zampino
authors.initials: Z
authors.lastname: Rosa
authors.affiliation: Department of Pediatrics, Second University of Naples, Naples, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Cirillo
authors.affiliation: Department of Clinical and Experimental Medicine and Surgery, Second University of Naples, Naples, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Stanzione
authors.affiliation: Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Macera
authors.affiliation: Internal Medicine and Hepatology, Second University of Naples, Naples, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Boemio
authors.affiliation: Department of Pediatrics, Second University of Naples, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Grandone
authors.affiliation: Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy.
authors.forename: Mariantonietta
authors.initials: M
authors.lastname: Pisaturo
authors.affiliation: Internal Medicine and Hepatology, Second University of Naples, Naples, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Marrone
authors.affiliation: Internal Medicine and Hepatology, Second University of Naples, Naples, Italy.
authors.forename: Luigi E
authors.initials: LE
authors.lastname: Adinolfi
authors.affiliation: Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy.
authors.forename: Evangelista
authors.initials: E
authors.lastname: Sagnelli
authors.affiliation: Department of Pediatrics, Second University of Naples, Naples, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Miraglia del Giudice
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D016014:Linear Models; D008049:Lipase / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D000998:Antiviral Agents; D008049:Lipase; D008565:Membrane Proteins; C419195:TM6SF2 protein, human; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
keywords: HCV infection; PNPLA3 polymorphism; TM6SF2 polymorphism; steatosis