{"title":"Prevalence of CYP2C19 Genetic Polymorphism among Normal People and Patients with Hepatic Diseases.","authors":"Z Hashemizadeh, S A Malek-Hosseini, P Badiee","doi":"","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Patients with hepatic diseases are treated with numerous drugs metabolized by cytochrome P450.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":14242,"journal":{"name":"International Journal of Organ Transplantation Medicine","volume":null,"pages":null},"PeriodicalIF":0.3000,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839627/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Organ Transplantation Medicine","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2018/2/1 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"TRANSPLANTATION","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
The International Journal of Organ Transplantation Medicine (IJOTM) is a quarterly peer-reviewed English-language journal that publishes high-quality basic sciences and clinical research on transplantation. The scope of the journal includes organ and tissue donation, procurement and preservation; surgical techniques, innovations, and novelties in all aspects of transplantation; genomics and immunobiology; immunosuppressive drugs and pharmacology relevant to transplantation; graft survival and prevention of graft dysfunction and failure; clinical trials and population analyses in the field of transplantation; transplant complications; cell and tissue transplantation; infection; post-transplant malignancies; sociological and ethical issues and xenotransplantation.