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Tumour necrosis factor-alpha gene polymorphism: implications in kidney transplantation
F Poli1, L Boschiero, F Giannoni
1Centro Trasfusionale e di Immunologia dei Trapianti, IRCSS Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy. nitpmi@polic.cilea.it
Cytokine
|December 1, 2000
Summary
Tumor Necrosis Factor-alpha (TNF-alpha) gene polymorphism in kidney transplant recipients is linked to transplant outcomes. High TNF-alpha producers experienced more acute rejection and graft failure.
Area of Science:
- Transplantation immunology
- Genetics
- Nephrology
Background:
- Tumor Necrosis Factor-alpha (TNF-alpha) is a key cytokine in immune responses.
- Genetic variations in the TNF-alpha gene may influence its production and impact transplant outcomes.
- Understanding these variations is crucial for predicting and managing post-transplant complications.
Purpose of the Study:
- To analyze the TNF-alpha biallelic polymorphism at the -308 position in kidney transplant recipients.
- To correlate TNF-alpha genotypes with post-transplant outcomes, including acute rejection and graft function.
- To investigate the relationship between TNF-alpha production phenotypes and clinical results.
Main Methods:
- Genotyping of 169 kidney recipients using polymerase chain reaction-sequence specific primer (PCR-SSP) methodology.
- Deduction of TNF-alpha phenotypes (low vs. high production) based on genotypes.
- Correlation of genotypes and phenotypes with clinical outcomes like acute rejection, vascular damage, and serum creatinine levels.
Main Results:
- A significant association was found between high TNF-alpha producer phenotypes and increased incidence of acute rejection episodes (P=0.048).
- High TNF-alpha producers also showed significantly higher rates of vascular damage (P=0.031) and elevated serum creatinine levels at 1 month (P=0.007).
- Logistic regression identified high TNF-alpha producer genotype and donor age as independent predictors of acute graft failure (P=0.02 and P=0.013, respectively).
Conclusions:
- Recipient TNF-alpha polymorphism at the -308 position is significantly associated with clinical outcomes in kidney transplantation.
- High TNF-alpha production, determined by specific genotypes, is linked to adverse post-transplant events, including acute rejection and graft failure.
- These findings suggest that TNF-alpha genetic variations could serve as a biomarker for predicting kidney transplant success.