Effect of Sirolimus Treatment on Gene Expression in Renal Transplant Patients

Abstract

Sirolimus (rapamycin), a strong immunosuppressive agent, is administered to renal transplant patients to prevent rejection. The rapamycin signaling pathway [mammalian target of rapamycin (mTOR)] has been implicated in transcriptional regulation. We used high-density oligonucleotide human microarrays to evaluate the effects of sirolimus treatment on gene expression in renal transplant patients. With this technique, we assessed selected genes in the rapamycin signaling, immunosuppression, insulin signaling, and triglyceride metabolism pathways. Filtered data from both treated and untreated patients showed variability within each group. Significant fold changes were observed in genes from the immunosuppression and insulin signaling pathways but not the rapamycin signaling pathway. The triglyceride metabolism pathway revealed a significant reduction of message levels in lipoprotein and triglyceride synthesis genes. These results show that using oligonucleotide microarrays to analyze the effects of sirolimus treatment in patients with renal transplant is an effective way to evaluate gene message levels in multiple pathways.