The tumor necrosis factor-α promoter correlates with progression of primary biliary cirrhosis

Atsushi Tanaka, Stefano Quaranta, Alberto Mattalia, Ross Coppel, Floriano Rosina, Michael Manns, M. Eric Gershwin

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Background/Aims: There have been many studies attempting to identify genes that determine susceptibility to primary biliary cirrhosis (PBC), but few studies have attempted to define the genes that modulate the natural history of the disease. There is a biallelic polymorphism, coined TNF1 and TNF2, in the TNFα promoter region at -308. We investigated the relative frequency of the TNF1 and TNF2 alleles in patients with PBC, based on the hypothesis that a polymorphism of the TNFα promoter region may be associated with the rate of progression and prognosis of PBC. Methods: Seventy-one Caucasoid patients with PBC and 133 healthy and unrelated Caucasoid individuals were studied. Genomic DNA was extracted from blood, and the mutation at position -308 of the TNFα gene analyzed by PCR and NcoI digestion. Results: In 71 patients with PBC, 56/71 (78.9%) patients were TNF1/TNF1 homozygotes, 14/71 (19.7%) were TNF1/TNF2 heterozygotes and 1/71 (1.4%) were TNF2/TNF2 homozygotes. In 133 healthy individuals, 109/133 (80.5%) patients were TNF1/TNF1 homozygotes, 24/133 (18%) were TNF1/TNF2 heterozygotes. No control individuals were TNF2/TNF2 homozygotes. The difference between the two groups was not statistically significant (p=0.3684). However, in patients with TNF1/TNF1 the Mayo score for disease severity was 4.596±0.157 (mean±SEM), compared to 5.637±0.420 for patients with TNF1/TNF2. This Mayo score was significantly higher in patients with the TNF1/TNF2 genotype than those with TNF1/TNF1 (p=0.0140), with an odds ratio of 4.9. Conclusions: Our data demonstrate that the presence of the TNF2 allele may be associated with a higher Mayo score, and thus with patients in a more advanced clinical stage. These data have both theoretical and clinical implications.

Original languageEnglish (US)
Pages (from-to)826-829
Number of pages4
JournalJournal of Hepatology
Volume30
Issue number5
DOIs
StatePublished - May 1999

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Biliary Liver Cirrhosis
Tumor Necrosis Factor-alpha
Homozygote
Heterozygote
Genetic Promoter Regions
Alleles
Genes
Digestion
Odds Ratio
Genotype
Polymerase Chain Reaction
Mutation
DNA

Keywords

  • Cholestasis
  • Primary biliary cirrhosis
  • TNFα
  • Transplantation

ASJC Scopus subject areas

  • Gastroenterology

Cite this

The tumor necrosis factor-α promoter correlates with progression of primary biliary cirrhosis. / Tanaka, Atsushi; Quaranta, Stefano; Mattalia, Alberto; Coppel, Ross; Rosina, Floriano; Manns, Michael; Gershwin, M. Eric.

In: Journal of Hepatology, Vol. 30, No. 5, 05.1999, p. 826-829.

Research output: Contribution to journalArticle

Tanaka, Atsushi ; Quaranta, Stefano ; Mattalia, Alberto ; Coppel, Ross ; Rosina, Floriano ; Manns, Michael ; Gershwin, M. Eric. / The tumor necrosis factor-α promoter correlates with progression of primary biliary cirrhosis. In: Journal of Hepatology. 1999 ; Vol. 30, No. 5. pp. 826-829.
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abstract = "Background/Aims: There have been many studies attempting to identify genes that determine susceptibility to primary biliary cirrhosis (PBC), but few studies have attempted to define the genes that modulate the natural history of the disease. There is a biallelic polymorphism, coined TNF1 and TNF2, in the TNFα promoter region at -308. We investigated the relative frequency of the TNF1 and TNF2 alleles in patients with PBC, based on the hypothesis that a polymorphism of the TNFα promoter region may be associated with the rate of progression and prognosis of PBC. Methods: Seventy-one Caucasoid patients with PBC and 133 healthy and unrelated Caucasoid individuals were studied. Genomic DNA was extracted from blood, and the mutation at position -308 of the TNFα gene analyzed by PCR and NcoI digestion. Results: In 71 patients with PBC, 56/71 (78.9{\%}) patients were TNF1/TNF1 homozygotes, 14/71 (19.7{\%}) were TNF1/TNF2 heterozygotes and 1/71 (1.4{\%}) were TNF2/TNF2 homozygotes. In 133 healthy individuals, 109/133 (80.5{\%}) patients were TNF1/TNF1 homozygotes, 24/133 (18{\%}) were TNF1/TNF2 heterozygotes. No control individuals were TNF2/TNF2 homozygotes. The difference between the two groups was not statistically significant (p=0.3684). However, in patients with TNF1/TNF1 the Mayo score for disease severity was 4.596±0.157 (mean±SEM), compared to 5.637±0.420 for patients with TNF1/TNF2. This Mayo score was significantly higher in patients with the TNF1/TNF2 genotype than those with TNF1/TNF1 (p=0.0140), with an odds ratio of 4.9. Conclusions: Our data demonstrate that the presence of the TNF2 allele may be associated with a higher Mayo score, and thus with patients in a more advanced clinical stage. These data have both theoretical and clinical implications.",
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T1 - The tumor necrosis factor-α promoter correlates with progression of primary biliary cirrhosis

AU - Tanaka, Atsushi

AU - Quaranta, Stefano

AU - Mattalia, Alberto

AU - Coppel, Ross

AU - Rosina, Floriano

AU - Manns, Michael

AU - Gershwin, M. Eric

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N2 - Background/Aims: There have been many studies attempting to identify genes that determine susceptibility to primary biliary cirrhosis (PBC), but few studies have attempted to define the genes that modulate the natural history of the disease. There is a biallelic polymorphism, coined TNF1 and TNF2, in the TNFα promoter region at -308. We investigated the relative frequency of the TNF1 and TNF2 alleles in patients with PBC, based on the hypothesis that a polymorphism of the TNFα promoter region may be associated with the rate of progression and prognosis of PBC. Methods: Seventy-one Caucasoid patients with PBC and 133 healthy and unrelated Caucasoid individuals were studied. Genomic DNA was extracted from blood, and the mutation at position -308 of the TNFα gene analyzed by PCR and NcoI digestion. Results: In 71 patients with PBC, 56/71 (78.9%) patients were TNF1/TNF1 homozygotes, 14/71 (19.7%) were TNF1/TNF2 heterozygotes and 1/71 (1.4%) were TNF2/TNF2 homozygotes. In 133 healthy individuals, 109/133 (80.5%) patients were TNF1/TNF1 homozygotes, 24/133 (18%) were TNF1/TNF2 heterozygotes. No control individuals were TNF2/TNF2 homozygotes. The difference between the two groups was not statistically significant (p=0.3684). However, in patients with TNF1/TNF1 the Mayo score for disease severity was 4.596±0.157 (mean±SEM), compared to 5.637±0.420 for patients with TNF1/TNF2. This Mayo score was significantly higher in patients with the TNF1/TNF2 genotype than those with TNF1/TNF1 (p=0.0140), with an odds ratio of 4.9. Conclusions: Our data demonstrate that the presence of the TNF2 allele may be associated with a higher Mayo score, and thus with patients in a more advanced clinical stage. These data have both theoretical and clinical implications.

AB - Background/Aims: There have been many studies attempting to identify genes that determine susceptibility to primary biliary cirrhosis (PBC), but few studies have attempted to define the genes that modulate the natural history of the disease. There is a biallelic polymorphism, coined TNF1 and TNF2, in the TNFα promoter region at -308. We investigated the relative frequency of the TNF1 and TNF2 alleles in patients with PBC, based on the hypothesis that a polymorphism of the TNFα promoter region may be associated with the rate of progression and prognosis of PBC. Methods: Seventy-one Caucasoid patients with PBC and 133 healthy and unrelated Caucasoid individuals were studied. Genomic DNA was extracted from blood, and the mutation at position -308 of the TNFα gene analyzed by PCR and NcoI digestion. Results: In 71 patients with PBC, 56/71 (78.9%) patients were TNF1/TNF1 homozygotes, 14/71 (19.7%) were TNF1/TNF2 heterozygotes and 1/71 (1.4%) were TNF2/TNF2 homozygotes. In 133 healthy individuals, 109/133 (80.5%) patients were TNF1/TNF1 homozygotes, 24/133 (18%) were TNF1/TNF2 heterozygotes. No control individuals were TNF2/TNF2 homozygotes. The difference between the two groups was not statistically significant (p=0.3684). However, in patients with TNF1/TNF1 the Mayo score for disease severity was 4.596±0.157 (mean±SEM), compared to 5.637±0.420 for patients with TNF1/TNF2. This Mayo score was significantly higher in patients with the TNF1/TNF2 genotype than those with TNF1/TNF1 (p=0.0140), with an odds ratio of 4.9. Conclusions: Our data demonstrate that the presence of the TNF2 allele may be associated with a higher Mayo score, and thus with patients in a more advanced clinical stage. These data have both theoretical and clinical implications.

KW - Cholestasis

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KW - Transplantation

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