title: PNPLA3 rs738409C/G polymorphism in cirrhosis: relationship with the aetiology of liver disease and hepatocellular carcinoma occurrence.
abstract: OBJECTIVE
  The PNPLA3 rs738409 C>G polymorphism has been found to be strongly associated with non-alcoholic fatty liver disease and with alcoholic liver disease. Whether the PNPLA3 rs738409 polymorphism could be a risk factor for the development of hepatocellular carcinoma (HCC) in cirrhosis patients is unknown.
  
  
  METHODS
  This study included 483 (344 males) consecutive Italian patients of Caucasian ethnicity affected by cirrhosis, of whom 279 had undergone transplantation for end-stage liver disease while 204 had been referred to our liver and transplant unit for the diagnosis of cirrhosis. The aetiologies were hepatitis C virus=209, hepatitis B virus=76, alcohol=166, metabolic=32. Ile148Met rs738409 transversion was genotyped using an restriction fragment length polymorphism-based assay.
  
  
  RESULTS
  The genotype frequencies of the rs738409 polymorphism were distributed differently in patients with cirrhosis C/C=168, C/G=220, G/G=95 vs controls C/C=218, C/G=175, G/G=35 (P<0.0001). Among cirrhotics, the G allele was over-represented in alcoholic/metabolic (0.505) vs viral (0.368, P<0.001) liver disease. Patients with cirrhosis complicated by HCC were more likely to be G/G homozygotes (38/141) than the remaining patients (57/342, P<0.02). At multivariate analysis, the PNPLA3 rs738409 polymorphism was confirmed to be an independent predictor of HCC occurrence (odds ratio 1.76, 95% confidence interval 1.06-2.92, P<0.05). HCC rates increased from 13/116 (11.2%; female C/(*) carriers), to 97/295 (32.9%; male C/(*) carriers and female G/G homozygotes), to 31/72 (43.1%; male G/G homozygotes) (P<0.0001).
  
  
  CONCLUSIONS
  The PNPLA3 rs738409 C>G polymorphism is associated with cirrhosis. In synergy with gender, this polymorphism is a strong predictor of HCC occurrence among patients with cirrhosis.
authors: Department of Medical Sciences Experimental and Clinical, University of Udine, Udine, Italy.
authors: Edmondo
authors: E
authors: Falleti
authors: Carlo
authors: C
authors: Fabris
authors: Sara
authors: S
authors: Cmet
authors: Annarosa
authors: A
authors: Cussigh
authors: Davide
authors: D
authors: Bitetto
authors: Elisabetta
authors: E
authors: Fontanini
authors: Ezio
authors: E
authors: Fornasiere
authors: Sara
authors: S
authors: Bignulin
authors: Elisa
authors: E
authors: Fumolo
authors: Eleonora
authors: E
authors: Bignulin
authors: Mario
authors: M
authors: Pirisi
authors: Pierluigi
authors: P
authors: Toniutto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics* / Q000821:virology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005234:Fatty Liver / Q000150:complications; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006509:Hepatitis B / Q000150:complications; D006526:Hepatitis C / Q000150:complications; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007558:Italy; D008049:Lipase / Q000235:genetics*; D008103:Liver Cirrhosis / Q000201:enzymology / Q000235:genetics* / Q000821:virology; D008104:Liver Cirrhosis, Alcoholic / Q000201:enzymology / Q000235:genetics* / Q000821:virology; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000821:virology; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; 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