title: Tumor necrosis factor gene polymorphisms and clearance or progression of hepatitis B virus infection.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. nirograzia@tiscalinet.it
authors.forename: Grazia Anna
authors.initials: GA
authors.lastname: Niro
authors.forename: Rosanna
authors.initials: R
authors.lastname: Fontana
authors.forename: Domenica
authors.initials: D
authors.lastname: Gioffreda
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Valvano
authors.forename: Angelo
authors.initials: A
authors.lastname: Lacobellis
authors.forename: Domenico
authors.initials: D
authors.lastname: Facciorusso
authors.forename: Angelo
authors.initials: A
authors.lastname: Andriulli
mesh_terms: 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*
chemical_list: D006510:Hepatitis B Antibodies; D014409:Tumor Necrosis Factor-alpha