The aim of this study was to determine whether IGF2 polymorphisms are associated with the clearance of hepatitis B virus (HBV) infection and the risk of hepatocellular carcinoma (HCC). A total of 1095 Korean subjects were prospectively enrolled in this case-control study. The rates of IGF2 polymorphisms were determined in each group. The IGF2 + 820E allele (IGF2 + 820G/G) and the IGF2 + 6815A/A genotype were strongly associated with the resolution of HBV infection (OR = 0.62-0.73; P = 0.001-0.03 and OR = 0.71; P = 0.03, respectively). Haplotype analysis showed that IGF2-haplotype5 (A-C-C-T-A-T-G) and IM-haplotypel (T-C-T-T-A-C-A) were significantly associated with the clearance and persistence of HBV infection (OR = 0.55-0.58, P = 0.009-0.01 and OR = 1.31-1.65, P = 0.001-0.007, respectively). On the other hand, the IGF2 + 2482C/C or +820G/G genotypes were significantly associated with a higher risk of HCC (OR = 1.88, 1.68; P = 0.04). IGF2 polymorphisms were found to be strongly associated with the clearance of HBV or the occurrence of HCC in patients with chronic HBV infection. (c) 2006 Elsevier Inc. All rights reserved.