Tumour necrosis factor-alpha gene polymorphism: Implications in kidney transplantation

In this study we have analysed the TNFA biallelic polymorphism at the - 308 position, in 169 kidney recipients that received the graft in a single Italian transplantation facility and we have then correlated the TNFA genotypes with the post-transplant outcome. To assess the cytokine genotypes, a polymerase chain reaction-sequence specific primer (PCR-SSP) methodology has been utilised. By the analysis of the different genotypes, the corresponding TNF-α phenotypes and the level of the TNF-α production, were deduced: the TNF*1/TNF*1 genotype gives a low TNF-α production level, TNF*1/TNF* 2 and TNF*2/TNF*2 genotypes give a high TNF-α production level. Out of the one hundred and sixty-nine patients studied, one hundred and twenty-one recipients (72%) had a low TNF-α producer phenotype, whereas forty-eight (28%) had a high TNF-α producer phenotype. These frequencies were not statistically different from those of the control group. The incidence of acute rejection episodes, vascular damage (grade III° of Banff classification), and serum creatinine levels at 1 month, were significantly greater in high TNF-α producers (P=0.048, 0.031 and 0.007 respectively). The logistical regression model indicated that only the high producer genotype and donor age were significantly and independently correlated with acute graft failure (P=0.02 and P=0.013 respectively). This analysis shows that recipient TNFA polymorphism, previously associated with differential production TNF-α by in vitro studies could be related to the clinical outcome of kidney transplantation.