title: Effect of PNPLA3 rs738409 variant (I148 M) on hepatic steatosis, necroinflammation, and fibrosis in Japanese patients with chronic hepatitis C.
abstract: BACKGROUND
  Host genetic factors have been suspected to influence histological liver damage in chronic liver disease. The nonsynonymous single-nucleotide polymorphism rs738409 C > G in the patatin-like phospholipase domain-containing 3 gene (PNPLA3, also known as adiponutrin), encoding the I148 M protein variant, has been identified as a novel genetic marker for hepatic steatosis and fibrosis in nonalcoholic fatty liver disease and alcoholic liver disease. We aimed to determine whether the PNPLA3 rs738409 variant was associated with hepatic steatosis, necroinflammation, and fibrosis in Japanese patients with chronic hepatitis C.
  
  
  METHODS
  In a cross-sectional study in Japan, we analyzed 276 patients with chronic hepatitis C who underwent liver biopsy. Genotyping for rs738409 was performed using the TaqMan genotyping assay.
  
  
  RESULTS
  The frequencies of the rs738409 CC, CG, and GG genotypes were 32.6, 46.4, and 21.0 %, respectively. Multivariate analysis revealed that the GG genotype was independently associated with the presence of steatosis [odds ratio (OR) 2.58, 95 % confidence interval (CI) 1.37-4.84, p = 0.003], severe necroinflammatory activity (OR 2.16, 95 % CI 1.12-4.16, p = 0.02), and advanced fibrosis (OR 2.10, 95 % CI 1.07-4.11, p = 0.03), after adjustment for age, sex, body mass index, and diabetes.
  
  
  CONCLUSIONS
  The PNPLA3 rs738409 variant influences histological liver damage in Japanese patients with chronic hepatitis C. The G allele homozygotes are at higher risk for hepatic steatosis, severe necroinflammation, and advanced fibrosis.
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kohichiroh
authors.initials: K
authors.lastname: Yasui
authors.forename: Takahisa
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Toshihide
authors.initials: T
authors.lastname: Shima
authors.forename: Hironori
authors.initials: H
authors.lastname: Mitsuyoshi
authors.forename: Kojiro
authors.initials: K
authors.lastname: Seki
authors.forename: Rei
authors.initials: R
authors.lastname: Sendo
authors.forename: Masayuki
authors.initials: M
authors.lastname: Mizuno
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Itoh
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okanoue
mesh_terms: D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D005234:Fatty Liver / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009336:Necrosis; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent