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

K. Sanghavi, R. C. Brundage, M. B. Miller, D. P. Schladt, A. K. Israni, W. Guan, W. S. Oetting, R. B. Mannon, R. P. Remmel, A. J. Matas, P. A. Jacobson

Research output: Contribution to journalArticlepeer-review

37 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

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