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Tumor necrosis factor-alpha promoter polymorphisms and the risk of rejection after liver transplantation: a case control analysis of 210 donor-recipient pairs
- Source :
- Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 9(4)
- Publication Year :
- 2003
-
Abstract
- After orthotopic liver transplantation (OLT), allograft rejection remains an important problem and is the major reason that immunosuppressive therapy must be administered. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory mediator that is central to the immune response, and intragraft expression of this cytokine is increased during acute cellular rejection (ACR). Polymorphisms within the TNF promoter have been identified and correlated with alterations in production. The aims of this study were to determine if an individual patient's propensity to develop ACR is related to the presence of these genetic polymorphisms (either alone or in combination) within donor and recipient tissue and to determine if these polymorphisms affect patient survival after OLT. The study group consisted of 210 patients who underwent OLT between 1989 and 1999 with at least 6 months survival, including 42 cases who had evidence of acute cellular rejection (biopsy-proven, elevated enzymes, and response to increased immunosuppression) and were matched 4:1 to controls (n = 168) with similar age, gender, underlying liver disease, date of transplant, and baseline immunosuppression. The underlying liver diseases were hepatisis C virus (HCV)/alcohol (70), HCV alone (50), alcohol (30), primary biliary cirrhosis (15), primary sclerosing cholangitis (15), autoimmune hepatitis/cirrhosis (10), cryptogenic (15), and hepatitis B virus (HBV) (5). DNA was extracted from paraffin-embedded donor and recipient liver tissue (total 420 samples), amplified, and sequenced for TNF single-nucleotide polymorphisms (TNFA-308 A/G and TNFA-238 A/G). We found no differences between the TNF allelic distributions among donors without liver disease (presumably representative of a normal control population) and patients with end-stage liver disease undergoing OLT. Multivariate analysis revealed no association with TNF polymorphisms (within donor or recipient tissue) and rejection risk or patient survival after transplantation. In this large case control analysis of patients undergoing liver transplantation for diverse etiologies, TNF promoter polymorphisms were not independently associated with rejection or survival.
- Subjects :
- Adult
Graft Rejection
Male
Heterozygote
Cirrhosis
Genotype
medicine.medical_treatment
Autoimmune hepatitis
Liver transplantation
Polymorphism, Single Nucleotide
Primary sclerosing cholangitis
Liver disease
Primary biliary cirrhosis
Gene Frequency
medicine
Humans
Genetic Predisposition to Disease
Promoter Regions, Genetic
Alleles
Aged
Transplantation
Hepatology
business.industry
Tumor Necrosis Factor-alpha
Homozygote
Immunosuppression
Middle Aged
medicine.disease
Survival Analysis
Tissue Donors
Liver Transplantation
Case-Control Studies
Immunology
Surgery
Female
business
Liver Failure
Subjects
Details
- ISSN :
- 15276465
- Volume :
- 9
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
- Accession number :
- edsair.doi.dedup.....4b6108aed08d3a1ddb66e3cb4861fe39