Dataset Information

Graft rejection: pharmacogenetic analysis or drug anamnesis?

ABSTRACT: AIMS: A 23-year-old Caucasian woman, with cystic fibrosis, bilateral lung-transplantation and immunosuppressive therapy with prednisolone, tacrolimus and sirolimus, presented with clinical symptoms of a chronic transplant rejection. METHODS: Since constant sufficient blood level of tacrolimus and sirolimus had never been achieved, a genetic analysis was carried out to clarify drug metabolism. RESULTS: The genetic analysis for polymorphisms of cytochrome P450 (CYP) 3A4,5,7 revealed no sequence alterations in the CYP 3A4,5,7 gene. Thus, drug intake was scrutinized in detail, disclosing a missing interval between the intake of both immunosuppressive agents. After a correct drug intake the woman's condition ameliorated and the blood levels reached normal range. CONCLUSIONS: This case report highlights the crucial importance of basic medical skills like an accurate and dainty drug anamnesis before high tech approaches were applied.

SUBMITTER: Pham VV

PROVIDER: S-EPMC2485220 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Graft rejection: pharmacogenetic analysis or drug anamnesis?

Pham V Vi VV Stichtenoth Dirk O DO Borlak Jürgen J

British journal of clinical pharmacology 20080313 6

<h4>Aims</h4>A 23-year-old Caucasian woman, with cystic fibrosis, bilateral lung-transplantation and immunosuppressive therapy with prednisolone, tacrolimus and sirolimus, presented with clinical symptoms of a chronic transplant rejection.<h4>Methods</h4>Since constant sufficient blood level of tacrolimus and sirolimus had never been achieved, a genetic analysis was carried out to clarify drug metabolism.<h4>Results</h4>The genetic analysis for polymorphisms of cytochrome P450 (CYP) 3A4,5,7 reve ...[more]

PMID: 18341681

Similar Datasets

Project description:Heart transplantation is the gold standard for treating patients with advanced heart failure. Although improvements in immunosuppressive therapies have significantly reduced the frequency of cardiac graft rejection, the incidences of T cell-mediated rejection (TCMR) and antibody-mediated rejection remain almost unchanged. A four-archetype analysis (4AA) model, developed by Philip F. Halloran, illustrated this problem well. It provided a new dimension to improve the accuracy of diagnoses and an independent system for recalibrating the histology guidelines. However, this model was based on the invasive method of endocardial biopsy, which undoubtedly increased the postoperative risk of heart transplant patients. Currently, little is known regarding the associated genes and specific functions of the different phenotypes. We performed bioinformatics analysis (using machine-learning methods and the WGCNA algorithm) to screen for hub-specific genes related to different phenotypes, based Gene Expression Omnibus accession number GSE124897. More immune cell infiltration was observed with the ABMR, TCMR, and injury phenotypes than with the stable phenotype. Hub-specific genes for each of the four archetypes were verified successfully using an external test set (accession number GSE2596). Logistic-regression models based on TCMR-specific hub genes and common hub genes were constructed with accurate diagnostic utility (area under the curve > 0.95). RELA, NFKB1, and SOX14 were identified as transcription factors important for TCMR/injury phenotypes and common genes, respectively. Additionally, 11 Food and Drug Administration-approved drugs were chosen from the DrugBank Database for each four-archetype model. Tyrosine kinase inhibitors may be a promising new option for transplant rejection treatment. KRAS signaling in cardiac transplant rejection is worth further investigation. Our results showed that heart transplant rejection subtypes can be accurately diagnosed by detecting expression of the corresponding specific genes, thereby enabling precise treatment or medication.

Dataset Information

Graft rejection: pharmacogenetic analysis or drug anamnesis?

Publications

Graft rejection: pharmacogenetic analysis or drug anamnesis?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets