Mycophenolate mofetil-related leukopenia in children and young adults following kidney transplantation: Influence of genes and drugs

Autor: Amy C. Wilson, Donald J. Weaver, Gina Marie Barletta, Scott K. Van Why, David K. Hooper, Rene G. VanDeVoorde, Cassie L. Kirby, Larry A. Greenbaum, Charles D. Varnell, Deepa H. Chand, Barry L. Warshaw, Priya S. Verghese, Alexander A. Vinks, Tsuyoshi Fukuda, Jens Goebel, Hiren P. Patel, Lisa J. Martin
Rok vydání: 2017
Předmět:
Genetic Markers
Male
medicine.medical_specialty
Adolescent
Single-nucleotide polymorphism
030230 surgery
030226 pharmacology & pharmacy
Polymorphism
Single Nucleotide
Article
03 medical and health sciences
Young Adult
0302 clinical medicine
Postoperative Complications
Internal medicine
hemic and lymphatic diseases
otorhinolaryngologic diseases
Medicine
Humans
Genetic Predisposition to Disease
Young adult
Adverse effect
Child
Genotyping
Kidney transplantation
Genetic Association Studies
Retrospective Studies
Transplantation
Leukopenia
business.industry
Incidence (epidemiology)
Incidence
Infant
Mycophenolic Acid
medicine.disease
Kidney Transplantation
Logistic Models
Case-Control Studies
Child
Preschool
Pediatrics
Perinatology and Child Health
Immunology
Female
medicine.symptom
business
Immunosuppressive Agents
circulatory and respiratory physiology
Zdroj: Pediatric transplantation. 21(7)
ISSN: 1399-3046
Popis: MMF is commonly prescribed following kidney transplantation, yet its use is complicated by leukopenia. Understanding the genetics mediating this risk will help clinicians administer MMF safely. We evaluated 284 patients under 21 years of age for incidence and time course of MMF-related leukopenia and performed a candidate gene association study comparing the frequency of 26 SNPs between cases with MMF-related leukopenia and controls. We matched cases by induction, steroid duration, race, center, and age. We also evaluated the impact of induction and SNPs on time to leukopenia in all cases. Sixty-eight (24%) patients had MMF-related leukopenia, of which 59 consented for genotyping and 38 were matched with controls. Among matched pairs, no SNPs were associated with leukopenia. With non-depleting induction, UGT2B7-900A>G (rs7438135) was associated with increased risk of MMF-related leukopenia (P = .038). Time to leukopenia did not differ between patients by induction agent, but 2 SNPs (rs2228075, rs2278294) in IMPDH1 were associated with increased time to leukopenia. MMF-related leukopenia is common after transplantation. UGT2B7 may influence leukopenia risk especially in patients without lymphocyte-depleting induction. IMPDH1 may influence time course of leukopenia after transplant.
Databáze: OpenAIRE
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