P- 12 pathogenic variant of pnpla3 does not associate with hepatocellular carcinoma in south americans. a report from the escalon network

Introduction and Objectives: Hepatocellular carcinoma (HCC) has a strong genetic component and single nucleotide polymorphisms (SNPs) have been consistently associated with HCC risk. Genetic variants in PNPLA3 have been shown to be frequent in South American populations related to non-alcoholic fatty liver disease (NAFLD). In Caucasian populations, the variant has been shown to increase the risk for HCC when included in Genetic Risk Scores (GRS). Whether this risk applies to other Latino or other populations is unclear. Materials and Methods: We analyzed blood samples of 217 HCC cases, 120 from South American patients (Argentina, Ecuador, Colombia, Chile and Peru) and 97 from Europeans (Netherlands), as well as 326 cirrhotic controls through the ESCALON network. Genotyping for PNPLA3 was performed using TaqMan-genotyping assay. Associations between HCC and each SNP were evaluated using logistic regression models. Results: The median age for HCC in South Americans was 68 y/o (IQR 62-72) and in Europeans, 69 y/o (IQR 60-74), with 59% and 69% of males, respectively. The etiology of liver disease was similar in both groups except for NAFLD/NASH, which accounted for 59% of Hispanics with HCC vs. 25% of Europeans. Proportions of the risk allele of PNPLA3 were more prevalent among Hispanics (90%) than Europeans (57%). PNPLA3 G/G was present in 22% of Europeans with HCC compared to 57% of Hispanics. The presence of 2 risk alleles for PNPLA3 was not associated with a higher risk of HCC in South Americans, OR 1.19 (CI 0.58-2.46) or Europeans OR 1.1o (CI 0.34-3.58). When PNPLA3 was added in a GRS with TM6SF2 and HSD17B13, calculating different allele combinations did not associate either with HCC in South Americans, Conclusions: Our results show that the prevalence of risk alleles in PNPLA3 differs between South Americans and Europeans. An SNP in PNPLA3 does not seem to confer an increased risk for HCC in South Americans.