Genotype-guided tacrolimus dosing in African-American kidney transplant recipients

DEKAF Investigators

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Tacrolimus is dependent on CYP3A5 enzyme for metabolism. Expression of the CYP3A5 enzyme is controlled by several alleles including CYP3A5∗1, CYP3A5∗3, CYP3A5∗6 and CYP3A5∗7. African Americans (AAs) have on average higher tacrolimus dose requirements than Caucasians; however, some have requirements similar to Caucasians. Studies in AAs have primarily evaluated the CYP3A5∗3 variant; however, there are other common nonfunctional variants in AAs (CYP3A5∗6 and CYP3A5∗7) that do not occur in Caucasians. These variants are associated with lower dose requirements and may explain why some AAs are metabolically similar to Caucasians. We created a tacrolimus clearance model in 354 AAs using a development and validation cohort. Time after transplant, steroid and antiviral use, age and CYP3A5∗1, ∗3, ∗6 and ∗7 alleles were significant toward clearance. This study is the first to develop an AA-specific genotype-guided tacrolimus dosing model to personalize therapy.

Original languageEnglish (US)
Pages (from-to)61-68
Number of pages8
JournalPharmacogenomics Journal
Volume17
Issue number1
DOIs
StatePublished - Jan 1 2017

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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