Association of TNF-α gene promoter polymorphisms with outcome of hepatitis B virus infection

Abstract

AIM: To investigate the polymorphism of tumor necrosis factor-α (TNF-α ) gene promoters in Chinese Han people, and to clarify whether such polymorphism was associated with the outcome of hepatitis B virus infection. METHODS: After the process of extracting genomic DNA from blood in 165 subjects who spontaneously recovered (SR) and 131 patients with chronic hepatitis B (CHB), four single nucleotide polymorphism (SNP) sites in TNF-α gene promoter marked as -238G/A, -308G/A, -857C/T and -863C/A were determined by polymerase chain reaction (PCR)- restriction fragment length polymorphism (RFLP) analysis. RESULTS: Twelve different promoter genotypes were de- tected from all of 296 research subjects, and GG·GG·CC·CC, GG·GG·CC·CA, GG·GG·CT·CC, GG·GA·CC·CC genotypes ac- counted for about 85% of genotypes in these subjects. By analyzing the four promoter genotypes of TNF-α , the re- sults showed that there were significant differences in the frequencies of GG·GG·CC·CC, GG·GG·CC·CA and GG·GA·CC· CC genotypes in TNF-α gene promoter between CHB and SR, GG·GG·CC·CC genotype carriers were at increased risk of CHB with an odds ratio of 2.15 (95% CI 1.34-3.45); While GG·GG·CC·CA and GG·GA·CC·CC genotypes carriers were at increased risk of CHB with an odds ratio of 0.48 (95% CI 0.27-0.86) and 0.35 (95% CI 0.14-0.89), respectively. GG·GG·CC·CA and GG·GA·CC·CC genotypes were strongly associated with the resolution of HBV infection (χ 2 =6.14, P =0.013<0.05; χ 2 =5.18, P =0.023<0.05, respectively). Single site analysis also revealed that TNF- α gene -308G/A and -863C/A SNP sites were associated with persistent HBV infection in Chinese Han people (-308G/ A site, χ 2 =6.53, P =0.011<0.05, OR=3.21; -863C/A site, χ 2 =4.33, P =0.037<0.05, OR=1.69, respectively).