The Genotype Frequency of CYP2C19 Enzyme after Liver Transplantation.

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.

Prevalence of CYP2C19 Genetic Polymorphism among Normal People and Patients with Hepatic Diseases.

BACKGROUND: Patients with hepatic diseases are treated with numerous drugs metabolized by cytochrome P450. OBJECTIVE: To evaluate the frequencies of CYP2C19 variant alleles (*2, *3, and *17), genotypes, and phenotypes, and the relationship between the frequency of these alleles and the underlying hepatic diseases among patients with advanced liver diseases who were candidates for liver transplantation. METHODS: The Study was conducted on 120 patients suffering from various hepatic disorders, candidates for liver transplantation, and 52 healthy volunteers. DNA was extracted from blood samples and analyzed by TaqMan SNP genotyping assay. The CYP2C19 genotypes were classified into poor, extensive, intermediate, and ultra-rapid metabolizer phenotypes. RESULTS: Viral hepatitis was the most common cause of liver disease among studied patients. The frequencies of CYP2C19 alleles *1, *17, and *2 were 66.7% (160/240), 20.8% (50/240) and 12.5% (30/240), respectively. Allele CYP2C19*3 was not found in the studied population. The most prevalent genotypes were CYP2C19 *1/*1 (47.5%) and *1/*17 (24.2%). The predicted CYP2C19 phenotypes were extensive metabolizer (47.5%), heterozygote extensive metabolizer (45.9%), ultra-rapid metabolizer (5%), and poor metabolizer (1.6%). There was no significant difference between the frequencies of CYP2C19 genotypes between healthy people and patients. The distribution of CYP2C19 genotype frequencies was not significantly associated with the underlying disease conditions (p=0.472). CONCLUSION: The distribution of CYP2C19 genotype frequencies in Iranian healthy people and patients with various hepatic diseases was not significantly different. This may allow the physicians to predict a tailoring dose regimens based on the individual's metabolic capacity, decrease the risk of harmful side effects of the drugs, and optimize the treatment.