Tumor necrosis factor gene polymorphisms and clearance or progression of hepatitis B virus infection
Article first published online: 20 SEP 2005
Volume 25, Issue 6, pages 1175–1181, December 2005
How to Cite
Niro, G. A., Fontana, R., Gioffreda, D., Valvano, M. R., Lacobellis, A., Facciorusso, D. and Andriulli, A. (2005), Tumor necrosis factor gene polymorphisms and clearance or progression of hepatitis B virus infection. Liver International, 25: 1175–1181. doi: 10.1111/j.1478-3231.2005.01166.x
- Issue published online: 11 NOV 2005
- Article first published online: 20 SEP 2005
- Received 11 March 2005, accepted 10 June 2005
- chronic hepatitis;
- TNF-α polymorphisms
Abstract: Objectives: We evaluated the influence of tumor necrosis factor-α (TNF-α) promoter gene polymorphisms on clearance of hepatitis B virus (HBV) and outcome of HBV chronic hepatitis.
Methods: Four TNF-α promoter polymorphisms (T-1031C, C-863A, G-308A, and G-238A) were evaluated by direct sequencing in 184 chronic HBV carriers hepatitis B surface antigen (HBsAg) positive and 96 controls with documented sero-clearance (HBsAg negativity, positivity for anti-HBs and anti-HBc IgG). Frequencies of single-nucleotide polymorphisms (SNPs) and haplotypes in the control group were compared with those of the chronic carrier group and with clinically defined subgroups of the latter: asymptomatic carriers, patients with compensated hepatitis, decompensated cirrhotics, and patients with hepatocellular carcinoma. Furthermore, subgroups of chronic carriers were compared among them.
Results: In the chronic carrier group, the −308G allele was more frequent in those with a family history of HBV infection (96% vs 88% of those with non-familial transmission). The G/G genotype at position −308 was found in all chronic carriers with decompensated cirrhosis but in only 78% of controls (P=0.01) and was more frequent in decompensated cirrhotics than in the other subgroups. The distribution of TNF-α gene polymorphisms in the carrier group was not significantly different from that in the sero-clearance control group. TNF-α SNPs at positions −1031/−863 and −863/−238 were in linkage disequilibrium. The TCGG haplotype (−T1031, −C863, −G308, −G238) was significantly associated with end-stage liver disease.
Conclusion: The TNF-α promoter polymorphisms do not appear to be determinant of HBV sero-clearance in southern Italians. The genotype −308G/G and haplotype TCGG are associated with an unfavorable prognosis in patients with chronic HBV infection.