Journal
LIVER INTERNATIONAL
Volume 31, Issue 8, Pages 1137-1143Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1478-3231.2011.02534.x
Keywords
cirrhosis; gender; genetic polymorphisms; hepatocellular carcinoma; PNPLA3
Categories
Funding
- 'Ricerca Sanitaria Finalizzata' Program, Regione Piemonte, Italy
- Fondazione CRUP Udine, Italy
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Background and aim: 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.
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