sábado, 2 de enero de 2016

The importance of MDR1 Gene polymorphisms for tacrolimus dosage. - PubMed - NCBI

2015 Dec 16. pii: S0928-0987(15)30094-4. doi: 10.1016/j.ejps.2015.12.020. [Epub ahead of print]

The importance of MDR1 Gene polymorphisms for tacrolimus dosage.

Kravljaca M1, Perovic V2, Pravica V2, Brkovic V3, Milinkovic M3, Lausevic M4, Naumovic R4.

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Abstract

Polymorphisms of multi drug resistance (MDR1) gene cause variability in P-glycoprotein mediated metabolism of tacrolimus. The aim of this study was to examine the relationship between MDR1 gene single nucleotide polymorphisms (SNPs) and its haplotypes with dosage of tacrolimus in kidney transplant recipients who were cytochrome (CYP) 3A5*3 homozygotes. This study included 91 kidney transplant recipients followed two years after transplantation. Detection and analysis of MDR1 gene polymorphisms in positions C1236T, G2677T/A and C3435T were performed using PCR method. Patients with variant alleles for SNPs G2677T/A and C3435T required higher doses of tacrolimus and had lower level/dose (L/D) ratio than patients with wild alleles or heterozygotes. That difference was the most obvious for SNP G2677T/A where TT homozygotes required significantly higher doses of tacrolimus during whole follow-up. Their L/D was significantly lower in the first month after transplantation. Recipients with CTT/TTT haplotype also had lower L/D than those with CGC/TTT and CGC/CGC, significantly in the 10th and 20th day after transplantation respectively (p<0.05). Our results demonstrate that TT homozygotes at positions G2677T/A and C3435T required a higher tacrolimus dose than those with wild alleles or heterozygotes. It may be helpful in the prevention of tacrolimus nephrotoxicity early after transplantation.