Objective: To investigate the association between the single nucleotide polymorphisms (SNPs) of tumor necrosis factor (TNF-alpha) and chronic severe hepatitis B.
Methods: Single nucleotide polymorphisms (SNPs) at TNF-alpha promoter -238 G/A, -308 G/A, -857 C/T, -863 C/A were analyzed in 98 patients with chronic severe hepatitis B and 211 patients with chronic hepatitis B in Beijing You'an hospital; using polymerase chain reaction and restriction fragment length polymorphism (RFLP-PCR).
Results: The rate of TNF-alpha -308 A and -857 T were 34.1% vs 9.5%, 34.7% vs 21.8% in the two grapes; the frequencies distributions of alleles at TNF-alpha -308 G/A, -857 C/T were significantly higher in patients with chronic severe hepatitis B than those of patients with chronic hepatitis B (chi(2) = 59.01, P = 0.000; chi(2) = 11.59, P = 0.001); genotypes of -308 GA, -857 TT were significantly higher in patients with chronic severe hepatitis B than those of patients with chronic hepatitis respectively (chi(2) = 28.06, P = 0.000; chi(2) = 19.69, P = 0.000). The frequencies of the alleles and the genotypes of TNF-alpha-238G/A,-863C/A did not differ significantly between the chronic severe hepatitis B groups and chronic hepatitis B groups respectively (chi(2) = 0.61, P = 0.436; chi(2) = 0.001, P = 0.976), (chi(2) = 1.16, P = 0.552; chi(2) = 0.63, P = 0.486). the -308 GA, -857 TT genotypes were associated with chronic severe hepatitis B respectively, OR reaches 4.176 (95% CI 2.416 - 7.216) and 6.09 (95% CI 2.652 - 14.001). The serum level of TNF-alpha were higher in patients with chronic severe hepatitis B than the patients with chronic hepatitis B (44 pg/ml +/- 47 pg/ml vs 10 pg/ml +/- 4 pg/ml; t = 3.951, P = 0.000).
Conclusion: The genetic polymorphisms at TNF-alpha sites are associated with the chronic severe hepatitis B and may play an important role on the progress of HBV infection as one of the host factors.