P Badiee1, Z Hashemizadeh2, S A Malek-Hosseini2, B Geramizadeh3. 1. Prof. Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. 2. Department of Organ Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. 3. Department of Pathology, Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Abstract
BACKGROUND: Liver transplant recipients are treated with various drugs, the metabolism of which is dependent on the cytochrome P450 polymorphic genotype. OBJECTIVE: To identify the polymorphic variety of CYP2C19 genotype in liver allograft before and after transplantation. METHODS: The study was conducted on 88 liver recipients. The CYP2C19 genotypes in donors and recipients were the same in 32 and different in 56 recipients. Extracted genomic DNA from the leukocytes and liver graft tissues were analyzed by TaqMan SNP genotyping assay. The distributions of homozygote, heterozygote, poor and ultra-rapid metabolizers' genotypes were investigated in both groups. RESULTS: The distributions of CYP2C19 genotypes before transplantation in the blood and liver graft were within the normal range. After transplantation, in patients with different CYP2C19 genotype in donors and recipients, the genotypes of homozygote and ultra-rapid metabolizers were significantly decreased (p=0.024); the heterozygotes and poor metabolizer genotypes were significantly increased (p=0.017). CONCLUSION: The variety in CYP2C19 genotyping must be considered in patients with different genotypes in donor and recipients to predict the dosage regimens, optimize the treatment and decrease toxicity.
BACKGROUND: Liver transplant recipients are treated with various drugs, the metabolism of which is dependent on the cytochrome P450 polymorphic genotype. OBJECTIVE: To identify the polymorphic variety of CYP2C19 genotype in liver allograft before and after transplantation. METHODS: The study was conducted on 88 liver recipients. The CYP2C19 genotypes in donors and recipients were the same in 32 and different in 56 recipients. Extracted genomic DNA from the leukocytes and liver graft tissues were analyzed by TaqMan SNP genotyping assay. The distributions of homozygote, heterozygote, poor and ultra-rapid metabolizers' genotypes were investigated in both groups. RESULTS: The distributions of CYP2C19 genotypes before transplantation in the blood and liver graft were within the normal range. After transplantation, in patients with different CYP2C19 genotype in donors and recipients, the genotypes of homozygote and ultra-rapid metabolizers were significantly decreased (p=0.024); the heterozygotes and poor metabolizer genotypes were significantly increased (p=0.017). CONCLUSION: The variety in CYP2C19 genotyping must be considered in patients with different genotypes in donor and recipients to predict the dosage regimens, optimize the treatment and decrease toxicity.
Authors: Reginald F Frye; Nathalie K Zgheib; Gary R Matzke; Diego Chaves-Gnecco; Mordechai Rabinovitz; Obaid S Shaikh; Robert A Branch Journal: Clin Pharmacol Ther Date: 2006-09 Impact factor: 6.875
Authors: H J Johnson; Kelong Han; B Capitano; D Blisard; S Husain; P K Linden; A Marcos; E J Kwak; B Potoski; D L Paterson; M Romkes; R Venkataramanan Journal: Antimicrob Agents Chemother Date: 2009-11-23 Impact factor: 5.191