Association Between The Tumor Necrosis Factor Gene Polymorphisms And The Clinical Types Of Patients With Chronic Hepatitis B Virus Infection

Objective To explore whether the polymorphisms within the tumor necrosis factor alpha (TNF-α) and TNF-β gene are associated with the clinical types of patients with chronic hepatitis B virus (HBV) infection.Methods 1. The TNF-α Concentrations of serum in 56 patients with chronic severe hepatitis B and 30 healthy controls were determined by radio immunity assay (RIA) and the correlation between the level of serum TNF-α and total bilirubin (TBIL) was analyzed.2. By using a restriction fragment length polymorphism (RFLP) assay of polymerase chain reaction (PCR) products, the single nucleotide polymorphisms (SNPs) within TNF-α and TNF-β gene among 56 patients with chronic severe hepatitis B and 71 patients with chronic mild hepatitis B or asymptomatic carriers as well as 90 healthy controls were analyzed. The levels of TNF-α and TBIL were compared among patients with chronic severe hepatitis B exhibiting different genotypes.Results 1. The TNF-α concentrations of serum in 56 patients with chronic severe hepatitis B were significantly higher than in 30 healthy controls (P<0.0l) and the level of serum TNF-α was significantly related to that of serum TBIL in patients with chronic severe hepatitis B(r=0.853, P<0.01).2. The frequencies of the TNF1/2 genotype and the TNF2 allele were significantly increased in patients with chronic severe hepatitis B compared with healthy controls(25%vsll.l%, P=0.028; 12.5%vs5.6%, P=0.036) and patients with chronic mild hepatitis B and asymptomatic carriers (25%vs8.8%, P=0.011; 12.5%vs4.2%, P=0.015). No difference of genotype distribution or allele frequency of TNF-α was found between patients with chronic mild hepatitis B and asymptomatic carriers and healthy controls.3. Heterozygotes carrying TNF2 allele had significantly higher levels of serum TNF-α than homozygotes for the wild type allele among all patients with chronic severe hepatitis B (P<0.05).4. The genotype distribution and allele frequency of TNF-β were similar between patients with chronic severe hepatitis B and healthy controls. However, the frequency of TNFβ*2/2 genotype in patients with chronic mild hepatitis B and asymptomatic carriers was significantly lower than in control subjects (9.9%vs22.4%, P=0.043) and patients with chronic sever hepatitis B (9.9%vs26.8%, P=0.043).5. There were no statistical differences in the levels of serum TNF-α and TBIL when comparisons were carried out among patients exhibiting different TNF-β genotypes with chronic severe hepatitis B.Conclusions 1. The TNF-α level of serum is related to the degree of necrosis of hepatocytes and can be used as a marker to evaluate patients' conditions and to predict prognosis.2. TNF gene polymorphisms were associated with the clinical types of patients with chronic HBV infection and may play an important role in the progress of HBV infection as one of the hosts' factor.