Tumour necrosis factor-α promoter region polymorphisms affect the course of spontaneous HBsAg clearance.
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.
Kao
Pei-Chi
PC
Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
Wu
Jia-Feng
JF
Ni
Yen-Hsuan
YH
Lin
Ying-Ting
YT
Chen
Huey-Ling
HL
Hsu
Sandy Huey-Jen
SH
Hsu
Hong-Yuan
HY
Chang
Mei-Hwei
MH
D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002478:Cells, Cultured; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006509:Hepatitis B / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D012075:Remission, Spontaneous; D018570:Risk Assessment; D012307:Risk Factors; D013624:Taiwan; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055815:Young Adult
D015415:Biomarkers; D006514:Hepatitis B Surface Antigens; D014409:Tumor Necrosis Factor-alpha