Tumour necrosis factor-α promoter region polymorphisms affect the course of spontaneous HBsAg clearance


Mei-Hwei Chang, MD, Department of Pediatrics, National Taiwan University Hospital; No. 8,Chung-Shan S. Rd., Taipei, Taiwan
Tel: +886 2 2312 3456, ext. 71718
Fax: +886 2 2311 4592
e-mail: changmh@ntu.edu.tw


Background: This study aimed to investigate the roles of tumour necrosis factor-α (TNF-α) gene polymorphisms in the spontaneous clearance of HBsAg after a hepatitis B virus (HBV) infection.

Methods: Polymorphisms in the TNF-α (−1031 T to C, −863 C to A, −857 C to T, −308 G to A and −238 G to A transition) gene were evaluated in 274 chronic HBV-infected patients and 194 patients with resolved HBV infection. The peripheral blood mononuclear cells (PBMC) isolated from 77 (28%) of the 274 chronic HBV-infected patients with negative HBeAg and positive antibody to HBeAg were stimulated with HBcAg. Data on TNF-α genotypes and phenotypes in subjects with/without the A allele at the TNF-α−863 promoter single nucleotide polymorphism (rs1800630) were compared.

Results: The A allele in the −863 promoter region of the TNF-α gene was present in 154 (56.2%) chronic HBV-infected patients and 87 (44.8%) patients who recovered from HBV infection (odds ratio 1.58; P<0.01). The TNF-α−863 A allele genotype predicted lower TNF-α production by PBMC after in vitro HBcAg stimulation (P<0.02).

Conclusions: The A allele at the −863 locus of the promoter region of the TNF-α gene predicts lower HBcAg-inducible TNF-α secretion. It is also associated with chronicity of HBV infection.