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Genetic polymorphisms influence mycophenolate mofetil-related adverse events in pediatric heart transplant patients

Erin L Ohmann1, Gilbert J Burckart, Maria M Brooks

  • 1Department of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania 15201, USA.

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
|January 12, 2010
PubMed
Abstract

Insights

Genetic variations in ABCC2, IMPDH1, and IMPDH2 influence adverse events like gastrointestinal intolerance and bone marrow toxicity in pediatric heart transplant patients receiving mycophenolate mofetil (MMF). This highlights the role of pharmacogenetics in MMF treatment.

Area of Science:

  • Pharmacogenetics
  • Immunosuppression Therapy
  • Pediatric Cardiology

Background:

  • Mycophenolate mofetil (MMF) is a widely used immunosuppressant with known adverse events.
  • Variability in patient response to MMF suggests a role for genetic factors.
  • Understanding these genetic influences is crucial for optimizing MMF therapy in pediatric heart transplant recipients.

Purpose of the Study:

  • To investigate the frequency of single nucleotide polymorphisms (SNPs) in IMPDH1, IMPDH2, and ABCC2 genes.
  • To determine if these specific SNPs are associated with adverse events in pediatric heart transplant patients on MMF.

Main Methods:

  • Genotyping of ABCC2 rs717620, IMPDH2 rs11706052, and IMPDH1 rs2288553, rs2288549, rs2278293, rs2278294, rs2228075 using TaqMan analysis.
  • Defining gastrointestinal (GI) intolerance based on symptoms and MMF treatment modifications.
  • Assessing bone marrow toxicity using standardized criteria (CTCAE v3).

Main Results:

  • Significant associations were found between specific SNPs and MMF-related adverse events.
  • The ABCC2 rs717620 A variant correlated with GI intolerance leading to MMF discontinuation (p < 0.001).
  • IMPDH1 variants (rs2278294 A, rs2228075 A) and IMPDH2 rs11706052 G variant were linked to increased GI intolerance and neutropenia, respectively.

Conclusions:

  • Specific genetic polymorphisms in ABCC2, IMPDH1, and IMPDH2 are associated with MMF-induced GI intolerance and bone marrow toxicity in pediatric heart transplant patients.
  • These findings suggest that pharmacogenetic profiling could potentially guide MMF treatment decisions.
  • Genetic factors play a significant role in the variability of MMF adverse event profiles.

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