Recently, two GWAS variants, MICA rs2596542 and DEPDC5rs1012068 were identified as being associated with the development of HCV-induced hepatocellular carcinoma (HCC) in Japanese patients.
SNPs in genes linked to HCC (DEPDC5, GRIK1, KIF1B, STAT4, MICA, DLC1, DDX18) or to liver damage (PNPLA3-rs738409, TM6SF2-rs58542926) in GWAS were genotyped in discovery cohorts including 1,020 HCC, 2,021 controls with chronic liver disease and 2,484 healthy individuals and replication was performed in prospective cohorts of cirrhotic patients with alcoholic liver disease (ALD, n = 249) and hepatitis C (n = 268).
Thus, DEPDC5 inactivation enhanced ROS resistance in HCC under the leucine-depleted conditions of chronic liver disease, contributing to poor patient outcome.
Recently, the MICA rs2596542 and DEPDC5rs1012068 variants in Japanese individuals as well as the HCP5 rs2244546 and PNPLA3 rs738409 variants in European individuals have been found associated with hepatocellular carcinoma (HCC).
Interestingly, these genetic variants also affect the activity of hepatitis, or disease progression in chronic hepatitis C. In addition, polymorphisms in apoptosis-related genes such as RNF7, TULP1, and MERTK are associated with fibrosis progression, and DEPDC5 and MICA variants are associated with HCV-related hepatocellular carcinoma.
This study was conducted to assess the association of DEPDC5 variants with advanced liver cirrhosis and HCC development among chronic HCV-infected patients in Saudi Arabian population.
Rs423058 upstream of PAPL, rs2834167 in IL10RB and rs1012068 in DEPDC5 were associated with chronic HBV status, HBV natural clearance and the presence of HCC (P = 0.0004–0.024), respectively.