title: A Variant in PNPLA3 Associated With Fibrosis Progression but not Hepatocellular Carcinoma in Patients With Hepatitis C Virus Infection.
abstract: OBJECTIVE
  A single nucleotide polymorphism (SNP) in the patatin-like phospholipase domain containing 3 gene (PNPLA3, rs738409) has been associated with fibrosis and development of hepatocellular carcinoma (HCC) in patients with nonalcoholic steatohepatitis, although its association with outcomes in patients with hepatitis C virus (HCV) infection is less clear. We evaluated the association between this SNP in PNPLA3 and fibrosis progression and development of HCC among HCV-infected patients.
  
  
  METHODS
  We performed a secondary analysis of data from participants in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial. Patients were randomly assigned to groups given weekly pegylated interferon or no further therapy for 3.5 y and then followed without further treatment until October 2009. Multivariate logistic regression was used to identify factors associated with fibrosis at baseline, fibrosis progression (defined as 2-point increase in Ishak score), and HCC development.
  
  
  RESULTS
  Among 937 HCV patients with known PNPLA3 genotype, 384 (41.0%) had cirrhosis at baseline. The PNPLA3 CG/GG SNP at rs738409 was significantly associated with the presence of cirrhosis (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.34-2.30), after adjusting for age, sex, diabetes, and race. Among 493 patients without cirrhosis at baseline who had at least 1 follow-up biopsy, 142 had fibrosis progression. In multivariate analyses, fibrosis progression was associated with obesity (OR, 1.67; 95% CI, 1.11-2.51) and the PNPLA3 CG/GG genotype (OR, 1.70; 95% CI, 1.13-2.56). PNPLA3 genotype was not associated with HCC development (P = .85). Using these data to update prior meta-analysis results, the rs738409 SNP in PNPLA3 was not significantly associated with development of HCC in HCV-infected patients (OR 1.29; 95% CI, 0.97-1.99).
  
  
  CONCLUSIONS
  Based on data from the HALT-C trial, the PNPLA3 CG/GG SNP at rs738409 is associated with fibrosis progression but not development of HCC in patients with HCV infection.
authors: Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas.
authors: Muhammad
authors: M
authors: Ali
authors: Department of Surgery, UT Southwestern Medical Center, Dallas, Texas.
authors: Adam
authors: A
authors: Yopp
authors: Department of Pathology, UT Southwestern Medical Center, Dallas, Texas.
authors: Purva
authors: P
authors: Gopal
authors: Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas.
authors: Muhammad S
authors: MS
authors: Beg
authors: Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas.
authors: Hao
authors: H
authors: Zhu
authors: Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas.
authors: William
authors: W
authors: Lee
authors: Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas; Department of Clinical Sciences, UT Southwestern Medical Center, Dallas, Texas. Electronic address: amit.singal@utsouthwestern.edu.
authors: Amit G
authors: AG
authors: Singal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005355:Fibrosis / Q000453:epidemiology* / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult; 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
keywords: Cirrhosis; HALT-C cohort; Hepatitis C; Liver cancer; Viral hepatitis; adiponutrin