A number of genetic loci have been proposed to be associated with persistent hepatitis B virus (HBV) infection. This study aimed to evaluate the association and interaction of susceptible genes with HBV persistence in a Chinese population. A total of 17 polymorphisms in 9 candidate genes were studied in 361 Chinese chronic hepatitis B patients and 304 patients who recovered spontaneously. Distributions of susceptible polymorphisms were examined in healthy Chinese and Caucasian populations. Gene-gene interactions were tested by the multifactor dimensionality reduction (MDR) method. The TNF -308 G/G genotype and G allele, IL-10RB codon 47 A allele, and MCP-1 -2518 G/G genotype and G allele were more frequent in patients than controls (P < 0.01, after multiple corrections Pc < 0.05), while the frequencies of TNF -308 A/G genotype and IL-10 -592 A/A genotype were significantly higher in controls than in the patient group (Pc < 0.05). The frequencies of the risk allele MCP-1 -2518 G and CTLA4 6230 G were much higher in Chinese than in the Caucasian groups (P < 0.001). An interaction between CCR5 -2459, TNFA -863, IL-10RB codon 47, and MCP-1 -2518 was detected by MDR (P = 0.001). The results indicate that genetic determinants may affect the outcome of HBV infection in both independent and synergic manners. J. Med. Virol. 82:371-378, 2010. (c) 2010 Wiley-Liss, Inc.