Tumor necrosis factor genetic polymorphsms correlate with infections afterliver transplantation

Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory mediator of t he immune response to allogenic and infectious stimuli, Non-immunosuppresse d individuals possessing a NcoI restriction enzyme site in the TNF gene loc us produce less TNF-alpha in vitro and in vivo compared with individuals la cking this restriction site. We performed polymerase chain reaction amplifi cation and restriction enzyme fragment length analysis of the TNF locus fro m 86 liver transplant recipients to determine if presence of the NcoI site is associated with the frequency of rejection or infection, time to rejecti on or infection, and patient and graft survival. We controlled for recipien t primary diagnosis, age, sex, United Network for Organ Sharing status, yea r of transplant, type of immunosuppression, use of anti-lymphocyte agents, and graft ischemia time. Fifty-six recipients possessed the NcoI+/low TNF-a lpha genotype and 30 were NcoI-/high TNF-alpha genotype, In the first year after transplant, there were no significant differences in the frequency, o r time to first rejections or the overall number of rejection episodes betw een the two genotypes. NcoI+/low TNF-alpha genotype recipients had signific antly more infections (1.52 vs. 0.87, P=0.014), In a linear regression, mul tivariate model controlling for all marginally significant variables, the N coI+/low TNF-alpha genotype was still associated with significantly more in fections (P=0.0031). Patient and graft survival were equal for the two grou ps. One implication of this study, in individuals genetically predetermined to be low TNF-alpha producers, is that additional inhibition of TNF-alpha production by routine immunosuppression may be excessive, rendering these i ndividuals less able to respond to infectious stimuli. These patients may b enefit from lower doses or withdrawal of corticosteroids.