title: TM6SF2 rs58542926 is not associated with steatosis and fibrosis in large cohort of patients with genotype 1 chronic hepatitis C.
abstract: OBJECTIVE
  We tested the putative association of the rs58542926 variant of TM6SF2, a recently described genetic determinant of nonalcoholic fatty liver disease, with steatosis and fibrosis in genotype 1(G1) chronic hepatitis C(CHC) patients.
  
  
  METHODS
  A total of 694 consecutively biopsied Caucasian G1 CHC patients were genotyped for TM6SF2 rs58542926, IL28B rs12979860 and PNPLA3 rs738409. Steatosis was classified as absent (<5%), mild-moderate(5-29%) and severe(≥30%), Fibrosis was considered severe if=F3-F4.
  
  
  RESULTS
  Carriers of TM6SF2 rs58542926 (6.3% of patients) exhibited lower serum levels of cholesterol (P = 0.04) and triglycerides (P = 0.01), but a similar distribution of steatosis severity (P = 0.63), compared to noncarriers. Prevalence and severity of steatosis were reduced in IL28B C allele carriers (P = 0.005) and elevated in PNPLA3 G allele carriers (P < 0.001). After adjustment for age, gender, body mass index and homoeostasis model assessment score, steatosis severity was independently associated with IL28B rs12979860 (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.55-0.86, P = 0.001) and PNPLA3 rs738409 (OR 1.84, 95% CI 1.46-2.83, P < 0.001), but not TM6SF2 rs58542926 (OR 1.48, 95% CI 0.82-2.69, P = 0.19). Variants of TM6SF2 (30.9% vs. 25%, P = 0.40), IL28B and PNPLA3 were not directly associated with fibrosis severity, although variants of IL28B and PNPLA3 promoted steatosis (OR 1.36, 95% CI 1.06-1.75, P = 0.01) that in turn is associated with severe fibrosis.
  
  
  CONCLUSIONS
  In G1 CHC patients, TM6SF2 rs58542926 does not affect the histological severity of liver damage. However, IL28B rs12979860 and PNPLA3 rs738409 modify steatosis.
authors.affiliation: Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Petta
authors.affiliation: Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Maida
authors.affiliation: Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Grimaudo
authors.affiliation: Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy.
authors.forename: Rosaria M
authors.initials: RM
authors.lastname: Pipitone
authors.affiliation: Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy.
authors.forename: Fabio S
authors.initials: FS
authors.lastname: Macaluso
authors.affiliation: Cattedra di Anatomia Patologica, University of Palermo, Palermo, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cabibi
authors.affiliation: Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy.
authors.forename: Calogero
authors.initials: C
authors.lastname: Cammà
authors.affiliation: Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Di Marco
authors.affiliation: Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Sferrazza
authors.affiliation: Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Craxì
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000453:epidemiology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D007558:Italy / Q000453:epidemiology; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D012720:Severity of Illness Index; D013223:Statistics as Topic; D000095022:Interferon Lambda; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D007372:Interferons; D007378:Interleukins; D008049:Lipase; D008565:Membrane Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C419195:TM6SF2 protein, human; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
keywords: CHC; IL28B; PNPLA3; TM6SF2; steatosis