Association of TNF-Alpha gene polymorphisms and susceptibility to hepatitis B virus infection in Egyptians

Tumor necrosis factor alpha (TNF-α) is one of the important cytokine in generating an immune response against hepatitis B virus (HBV). Genetic polymorphisms might influence gene transcription, leading to disturbance in cytokine production. We hypothesized that single nucleotide polymorphism (SNPs) in TNF-α gene could affect the pathogenesis of HBV. To test this hypothesis, we investigated the role of TNF-α polymorphism [−863C/A (rs1800630), −308G/A (rs1800629), −376G/A (rs1800750), −857C/T (rs1799724) and +489G/A (rs1800610)] in the susceptibility to chronic hepatitis B (CHB) infection. Polymorphisms of the TNF-α (−863C/A (rs1800630), −308G/A) were analyzed by Polymerase chain reaction sequence specific primer (PCR-SSP) while TNF-α (−376G/A, −857C/T and +489G/A) by PCR-restriction fragment length polymorphism (PCR-RFLP) in 104 patients with CHB and 104 healthy controls. The plasma level of TNF-α was measured using Enzyme-linked immunosorbent assay (ELISA). The study showed a significant increase in the frequency of −863CC, −376GA, −857CC, −857TT and +489GA genotypes and −863C, −376A, −857C, and +489A alleles in CHB patients compared to controls. In addition, CAGCG haplotype had a highest frequency in CHB patients. A strong Linkage Disequilibrium (LD) between TNF-α −863C/A (rs1800630) and −376G/A (D′ = 0.7888, r2 = 0.0200); −308G/A and −857C/T (D′ = 0.9213, r2 = 0.1770); −308G/A and +489G/A (D′ = 0.9088, r2 = 0.1576) was demonstrated. CHB patients had significantly lower levels of TNF-α compared to controls. In conclusion, our preliminary results suggest that −863C/A (rs1800630), −308G/A, −376G/A, and +489G/A of the TNF-α gene may play a role in HBV susceptibility in Egyptians. The significant reduction in TNF-α in CHB patient was independent of any particular genotype/haplotype in TNF-α.