CYP3A4 Polymorphisms and Acute Cellular Rejection in Lung Transplant Patients

Abstract

Purpose Tacrolimus is the main component of the immunosuppressive regimen used in patients with solid organ transplants. Genetic polymorphism in CYP3A4 and CYP3A5 enzyme expression contributes to differences in tacrolimus metabolism with potential impact on allograft function. Although genetic factors influencing immunosuppressive response have been studied in kidney, heart and liver transplant patients, data regarding lung transplant patients are more limited. The aim of our study was to determine the relationship between CYP3A4 and CYP3A5 polymorphisms and acute rejection. Methods 41 lung transplant recipients were included. We retrospectively reviewed clinical and pathology data of patients. CYP3A5 polymorphisms were defined as intermediate, normal, or poor metabolizers. CYP3A4 polymorphisms were defined as rapid, intermediate, normal, or poor metabolizers. The diagnosis of acute cellular rejection was based on histopathology results. Chi-square statistic was used to compare categorical continuous variables (CYP3A5, CYP3A4 and acute rejection). Results The mean age of the patients was 59±13 years (mean ± SD) with an age range between 21 to 75 years. Among patients included in the analysis there were 51% males . There was a statistically significant increased rate of rejection in patients with normal CYP3A4 polymorphisms (68%) as compared to patients with poor and intermediate CYP3A4 polymorphisms (20%) (p 0.036). There was no association between CYP3A5 phenotype and acute rejection (p= 0.33). Conclusion Although this was a small study, our data suggest that CYP3A4 phenotype may influence the occurrence of acute rejection. Patients with normal CYP3A4 phenotype might require closer monitoring and higher tacrolimus concentrations to avoid rejection. Additional studies are needed to confirm these results and determine whether genotype-based tacrolimus dosing could improve outcomes in lung transplant recipients.