Association of TNF-α Gene Polymorphisms with Production of Protein and Susceptibility to Chronic Hepatitis B Infection in the South East Iranian Population

Abstract

Background: The host genetic background regulates the natural history of chronic hepatitis B virus (HBV) infection.

Objectives: The aim of this study was to investigate the association between TNF-α gene polymorphism in the promoter region and susceptibility to chronic hepatitis B virus infection.

Methods: Four polymorphisms of TNF-α gene including -238 A/G, -308 A/G, -857 C/T, and -863 A/C were analyzed by PCR-RFLP in 100 chronic HBV infected patients (HBV group), 40 spontaneously recovered HBV subjects (SR group), and 100 healthy controls (C group). Also, serum levels of protein were monitored.

Results: The study showed that the existence of -308 G, -857 C, and -863 A alleles significantly increased susceptibility to chronic HBV infection. In addition, GGCA haplotype had a higher frequency in HBV patients than C and SR groups that might be related to the natural history of the infection. Chronic HBV patients with -308 GG, -857 CC, and -863 AA genotypes had lower serum levels of TNF-α compared to those with other genotypes.

Conclusions: The results indicated that there was a positive association between susceptibility to chronic HBV infection and TNF-α polymorphism. In addition, HBV patients carrying -308 GG, -857 CC, and -863 AA genotypes with lower serum levels of TNF-α had an increased risk of infection.

Keywords: Chronic Hepatitis B Virus; Gene; Polymorphism; Tumor Necrosis Factor-a.

Figure 1.. The Electrophoresis Pattern of TNF-α -238 A/G, -308 A/G, -857 C/T, and -863 A/C Polymorphisms

(A), The digestion pattern of Msp I restriction enzyme on 4% agarose gel at -238 A/G SNP; M marker 100bp, 1 genotype AA, 2 genotype AG, 3 genotype GG; (B), The digestion pattern of NcoI restriction enzyme on 4% agarose gel at -308 A/G SNP; M marker 100bp,1 genotype AA, 2 genotype AG, 3 genotype GG; (C), The digestion pattern of HincII restriction enzyme on 4% agarose gel at -857 C/T SNP, M marker 100 bp,1 genotype TT, 2 genotype CT, 3 genotype CC; (D), The digestion pattern of StyI restriction enzyme on 4% agarose gel at -863 A/C SNP; M marker 100bp,1 genotype AA, 2 genotype AC, 3 genotype CC.