CYP3A5*3 and CYP2C8*3 variants influence exposure and clinical outcomes of tacrolimus-based therapy

Fabiana Dalla Vecchia Genvigir, Antony Brayan Campos-Salazar, Claudia Rosso Felipe, Helio Tedesco-Silva, José Osmar Medina-Pestana, Sonia de Quateli Doi, Alvaro Cerda, Mario Hiroyuki Hirata, María José Herrero, Salvador Francisco Aliño, Rosario Dominguez Crespo Hirata
Pharmacogenomics 2020, 21 (1): 7-21
Aim: The influence of variants in pharmacokinetics-related genes on long-term exposure to tacrolimus (TAC)-based therapy and clinical outcomes was investigated. Patients & methods: Brazilian kidney recipients were treated with TAC combined with everolimus (n = 178) or mycophenolate sodium (n = 97). The variants in CYP2C8 , CYP2J2 , CYP3A4, CYP3A5 , POR , ABCB1 , ABCC2, ABCG2 , SLCO1B1 and SLCO2B1 were analyzed. Main results: CYP3A5*3/*3 genotype influenced increase in TAC concentration from week 1 to month 6 post-transplantation (p < 0.05). The living donor and CYP2C8*3 variant were associated with reduced risk for delayed graft function (OR = 0.07; 95% CI = 0.03-0.18 and OR = 0.45; 95% CI = 0.20-0.99, respectively, p < 0.05). Conclusion: The CYP3A5*3 variant is associated with increased early exposure to TAC. Living donor and CYP2C8*3 variant seem to be protective factors for delayed graft function in kidney recipients.

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