PNPLA3 I148M polymorphism, etiology, and clinical features of hepatocellular carcinoma

Background & Aims : Recently, the Patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 C>G single nucleotide polymorphism (SNP), encoding for the I148M protein variant, has been recognized as a genetic determinant of liver fat content and to influence severity of liver damage in patients with non-alcoholic and alcoholic fatty liver disease (NAFLD and ALD) and with chronic hepatitis C (CHC). Furthermore, homozygosity for the148M allele has been associated with hepatocellular carcinoma (HCC) in CHC. Aim of the study was to evaluate the prevalence of the PNPLA3 148M variant in Italian patients with HCC and the influence on the natural history liver cancer. Patients and Methods: We studied 265 consecutive patients (M/F 203/62, age 68\ub19 yrs) with HCC referred to tertiary care centres in Italy with available DNA samples. HCC arose during follow up in 207 and was incidental in the remaining 58, in 5 cases HCC occurred in non-cirrhotic liver, and was diagnosed according to EASL criteria. The rs738409 genotype was determined by a Taqman assay. Results: The frequency distribution of the rs738409 SNP was 113 p.148I/I (45%), 119 p.148I/M (47%), and 33 (13%) p.148G/G (p