*Purpose: Tacrolimus has always been dosed based on therapeutic drug monitoring, however pharmacogenomics is becoming increasingly more utilized in the era of precision based medicine and is starting to be incorporated into tacrolimus dosing considerations. Consensus guidelines are available recommending increased tacrolimus dose requirements in patients who have intermediate or extensive CYP3A5 metabolism phenotypes. CYP3A4*22 allele carriers have also been shown to have decreased tacrolimus metabolism. Historically, genetic heterogeneity has been generalized between different ethnic groups, i.e., “African populations have lower frequencies of CYP3A5*3 allele”, or “Asian populations have lower CYP2C19 activity”. With the advent of more widely available genetic assays that report individual genetic makeup, it may no longer be appropriate to generalize genetic differences between ethnic groups and instead we should consider heterogeneity within them. We report the CYP3A4 and CYP3A5 polymorphisms among Caucasian kidney transplant recipients.

*Methods: RxMatch® is a DNA testing assay that provides individual information about CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, and CYP4F2 expression. RxMatch® was obtained by cheek swab in the pre-transplant phase during clinic visits. Adult patients who received a kidney transplant at Intermountain Medical Center between June 2017 and Oct 2019 and had RxMatch® testing were included.

*Results: 60 Caucasian kidney transplant recipients received RxMatch® testing. With regards to CYP3A4 activity, 5 patients (8.3%) were classified as intermediate metabolizers based on polymorphisms containing either *1A|*22 or *1B|*22 alleles, and 55 patients (91.6%) had normal activity containing either *1A|*1A or *1A|*1B alleles. Concerning CYP3A5 activity, 49 patients (81.6%) were classified as poor metabolizers containing either *3A|*3A, *3C|*3C, *3A|*3C, *3B|*3C, or *3A|*3B alleles, and 11 patients (18.3%) were classified as intermediate metabolizers containing either *1D|*3A, *1A|*3C, *1A|*3A, or *1D|*3C alleles. 10 patients in this cohort (16.6%) had biopsy proven acute rejection in the first year post transplant; 1 was an intermediate CYP3A4 metabolizer, 1 was an intermediate CYP3A5 metabolizer, and 8 had normal CYP3A4/poor CYP3A5 activity. Intermediate metabolizers exhibited significantly lower tacrolimus troughs on POD1.

*Conclusions: There is considerable heterogeneity within the Caucasian kidney transplant population at our center concerning CYP3A4 and CYP3A5 activity, including genotypes that significantly affect tacrolimus metabolism and dosing. Our results suggest that therapeutic drug monitoring and individualized initial dosing of tacrolimus are better served by pharmacogenetics stratification rather than by broad generalizations based on self-declared race or ethnicity.

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