Tumor necrosis factor gene polymorphisms and clearance or progression of hepatitis B virus infection.
OBJECTIVE
We evaluated the influence of tumor necrosis factor-alpha (TNF-alpha) promoter gene polymorphisms on clearance of hepatitis B virus (HBV) and outcome of HBV chronic hepatitis.


METHODS
Four TNF-alpha 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 -308 G 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-alpha gene polymorphisms in the carrier group was not significantly different from that in the sero-clearance control group. TNF-alpha 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.


CONCLUSIONS
The TNF-alpha 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.
Niro
Grazia Anna
GA
Department of Gastroenterology, Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. nirograzia@tiscalinet.it
Fontana
Rosanna
R
Gioffreda
Domenica
D
Valvano
Maria Rosa
MR
Lacobellis
Angelo
A
Facciorusso
Domenico
D
Andriulli
Angelo
A
D002353:Carrier State; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006510:Hepatitis B Antibodies / Q000097:blood; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D006510:Hepatitis B Antibodies; D014409:Tumor Necrosis Factor-alpha