Role of cytokine gene polymorphisms in acute rejection and renal impairment after liver transplantation

Although immunosuppressive regimens are effective, rejection occurs in up t o 50% of patients after orthotopic liver transplantation (OLT), and there i s concern about side effects from long-term therapy. Knowledge of clinical and immunogenetic variables may allow tailoring of immunosuppressive therap y to patients according to their potential risks. We studied the associatio n between transforming growth factor-beta, interleukin-10, and tumor necros is factor alpha (TNF-alpha) gene polymorphisms and graft rejection and rena l impairment in 121 white liver transplant recipients. Clinical variables w ere collected retrospectively, and creatinine clearance was estimated using the formula of Cockcroft and Gault. Biallelic polymorphisms were detected using polymerase chain reaction-based methods. Thirty-seven of 121 patients (30.6%) developed at least 1 episode of rejection. Multivariate analysis s howed that Child-Pugh score (P =.001), immune-mediated liver disease (P =.0 18), normal pre-OLT creatinine clearance (P =.037), and fewer HLA class 1 m ismatches (P =.038) were independently associated with rejection, Renal imp airment occurred in 80% of patients and was moderate or severe in 39%, Clin ical variables independently associated with renal impairment were female s ex (P =.001), pre-OLT renal dysfunction (P =.0001), and a diagnosis of vira l hepatitis (P =.0008), There was a significant difference in the frequency of TNF-alpha -308 alleles among the primary liver diseases. After adjustme nt for potential confounders and a Bonferroni correction, the association b etween the TNF-alpha -308 polymorphism and graft rejection approached signi ficance (P =.06). Recipient cytokine genotypes do not have a major independ ent role in graft rejection or renal impairment after OLT, Additional studi es of immunogenetic factors require analysis of large numbers of patients w ith appropriate phenotypic information to avoid population stratification, which may lead to inappropriate conclusions.