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Increased Hospital Stay and Allograft Disfunction in Renal Transplanted Patients with CYP2C19 AA Variant in SNP RS4244285.


Drug Metab Dispos. 2012 Nov 21;


Authors: Boso V, Herrero MJ, Bea S, Galiana M, Marrero P, Marques MR, Hernandez J, Sanchez-Plumed J, Poveda JL, Alino SF


Abstract

Pharmacogenetics correlates certain genetic variants, as Single Nucleotide Polymorphisms, SNPs, with blood drug levels, efficacy and adverse effects of the treatment. Tacrolimus is mainly metabolized via CYP3A4/5, whereas CYP2C19 and CYP3A4/5 are responsible of omeprazole metabolism. Omeprazole inhibits tacrolimus metabolism via CYP3A5 in patients carrying variant alleles of CYP2C19, increasing tacrolimus blood concentrations. 75 renal transplanted patients, treated with tacrolimus and concomitant omeprazole, were genotyped in a panel of 37 SNPs employing Sequenom® MassArray. The patients with CYP2C19*2/*2 genotype (n=4) showed a post-transplantation hospital stay of 27.5 days (median, 95% CI: 23-39) against 12 days (median, 95%CI: 10-15) in patients CYP2C19*1/*1 or *1/*2 (n=71), (p=0.016, Kruskal-Wallis test).The difference in hospital stay was directly correlated with an increase in tacrolimus levels Cmin/(dose/weight), during the first week post-trasplantation (in 59 patients with levels data) (p=0.021, Kruskal-wallis), excluding the patients with atypical metabolisms due to CYP3A5*1/*3 or *1/*1 genotype. Recipients with CYP2C19*2/*2 genotype also showed allograft delayed function (acute tubular necrosis in 3 of them). Genotyping of CYP3A5 and CYP2C19 in renal transplantation should be considered of interest, when treating with tacrolimus and omeprazole since CYP2C19*2/*2 variant indirectly elicits an increase of tacrolimus blood levels and, in our study population, the adverse effects described.

PMID: 23175667 [PubMed - as supplied by publisher]