CYP2C19 polymorphism is associated with pretreatment drug response prediction, metabolism, and disposition. Pakistan consists of a population comprising of various ethnic groups residing in different regions of the country each claiming diverse ethnic origins. The identification of CYP450 genotypic composition of these populations is therefore necessary to avoid adverse drug reactions in these individuals. The main objective of the study was to investigate the prevalence of CYP2C19*2 and CYP2C19*17 alleles in these ethnic groups. The study was conducted on one thousand and twenty-eight (n = 1028) healthy volunteers from nine ethnic groups of Pakistan namely Brusho (n = 28), Hazara (n = 102), Kalash (n = 64), Pathan (n = 170), Punjabi (n = 218), Saraiki (n = 59), Brahui (n = 118), Parsi (n = 90), and Sindhi (n = 179). DNA was extracted from leukocytes and analyzed by allele specific amplification polymerase chain reaction (ASA-PCR). Multi allelic polymorphism of CYP2C19 led to four distinct phenotypes identified as extensive metabolizer (EM), poor metabolizer (PM), intermediate metabolizer (IM), and ultra-rapid metabolizer (UM). Over all, the percentage of predicted poor metabolizer allele was 29. 0% compared to UM allele (23. 70%). Among the studied groups, Saraiki and Brahui showed highest percentage of PM allele (40%, 36%) whereas Parsi and Hazara had highest percentage of UM allele (37% and 30% respectively). In conclusion, the high allele frequency of PM (CYP2C19*2 and *17) in Pakistani population led to the recommendation of a pre-treatment test to monitor drug response and dosage (personalized medicine) to avoid post-treatment adverse drug reactions.

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.

Introduction: Since there has been a dearth of research on the assessment of CYP2C19 polymorphism in the east of Iran (Khorasan provinces), this study aimed to detect, CYP2C19*2 and CYP2C19*3 allele frequencies among patients with coronary artery disease. The participants were selected among those referring to Emam Reza Hospital, Mashhad, Iran. Furthermore, the current research was motivated to elucidate the association of CYP2C19 polymorphism with the severity and pattern of coronary artery disease. Material and Methods: This study was conducted on 84 patients who were subjected selective coronary angiography. The participants of the present study were from Khorasan, Iran. The Genotyping of extracted crude DNA for CYP2C19*2 (rs4244285) and CYP2C19*3 (rs4986893) alleles was performed through PCR-RFLP method. Results: The obtained results of the current study revealed three different allelic band patterns. Out of the 84 individuals, 71 were homozygous for the wild type allele in both exon 5 and exon 4 (wt/wt; 84. 5%), 15 were homozygous for the CYP2C19*2 polymorphism (*2/*2; 14. 3%), and 1 subject was homozygous for the CYP2C19*3 (*3/*3; 1. 2%). No subjects were heterozygous for the CYP2C19*2 (wt/*2; 0. 0%) or CYP2C19*3 (wt/*3; 0. 0%) or heterozygous for the CYP2C19*2 and the CYP2C19*3 mutations (*2/*3; 0. 0%). Conclusion: The findings of the current study confirmed the existence of CYP2C19 polymorphism among people of Khorasan.

Background: Cytochrome P450 2C19 (CYP2C19) is widely involved in the metabolism of some medications. On the other hand, recent studies have shown the contribution of the CYP2C19 polymorphisms to different malignancies. We aimed to investigate the association between CYP2C19 polymorphism and occurrence of hematological malignancies by comparing the phenotype distribution of this enzyme in patients and healthy subjects. Methods: 150 Iranian patients with hematological malignancies from different ethnicities were recruited. Mutant alleles of the CYP2C19*2 and *3 were examined using PCR-RFLP technique and CYP2C19*17 was genotyped using DNA sequencing analysis. Results: CYP2C19*17 was the most common allelic variation (24%, 95% CI: 19. 17-28. 83%) among patients with hematological malignancies, whereas the variant CYP2C19*3 was not detected among our patients. Furthermore, the CYP2C19*1*1 and CYP2C19*1*17 genotypes which respectively represented the “ extensive metabolizer” (EM) and Ultra-rapid metabolizer (URM) phenotypes, had the highest incidence. Conclusion: The results of this study suggested that there may be no association between CYP2C19 polymorphisms and occurrence of hematological malignancies. However, larger well-designed studies are necessary to confirm these results in Iranian populations.

BACKGROUND: The polymorphisms of cytochrome P450 2C19 (CYP2C19) gene are major prognostic factors for the response to clopidogrel therapy in patients with coronary artery diseases (CAD). The CYP2C19*2 is the most important allele responsible for resistance to clopidogrel therapy. This study examined CYP2C19 gene polymorphism (CYP2C19*1 and *2) in Iranian patients.METHODS: This cross-sectional study was performed on 43 Iranian patients with CAD who underwent percutaneous coronary intervention (PCI) and received drug-eluted stents (DES).CYP2C19 polymorphisms were assessed using real time PCR and frequency of CYP2C19*1 and CYP2C19*2 were determined, and then homo- or heterozygous state of genes was detected by Melt Curve Analysis method.RESULTS: Forty three patients (mean age=58.8±10.0 years, 79.1% male) participated in this study. CYP2C19*1/CYP2C19*1 genotype was observed in 31 (72.1%) of participates, CYP2C19*1/CYP2C19*2 genotype in 10 (23.3%), and CYP2C19*2/CYP2C19*2 genotype in 2 patients (4.7%). The frequency of CYP2C19*2 allele in the sample was 27.9%.CONCLUSION: This study demonstrated a high prevalence of CYP2C19*2 gene polymorphism in Iranian patients. Further studies with larger samples or longitudinal are required to determine the effects of this polymorphism on the prognosis of CAD patients in our population.

BACKGROUND AND AIM: Cytochrome P450 2C19 (CYP2C19) is a polymorphically expressed enzyme that shows marked interindividual and interethnic variation. CYP2C19*2 and CYP2C19*3 are the most frequent identified defective alleles in Orientals and Caucasian poor metabolizers (PM).The aim of this study was to investigate the frequencies of CYP2C19*1, CYP2C19*2 and CYP2C19*3 alleles and CYP2C19 genotypes among Mazandarani ethnic group among Iranian Population.METHODS: The study was conducted on 103 unrelated healthy volunteers. DNA was extracted from leucocytes and analyzed by the PCR-RFLP protocol. The PCR product was digested with restriction enzymes (SmaI and BamH1) and then separated electrophoretically using polyacrylamide gel.RESULTS: Of the tested alleles, CYP2C19*1, and CYP2C19*2, but not CYP2C19*3, were detected. The frequencies for CYP2C19 alleles *1, *2, and *3 were 91%, 9.0%, and 0.0%, respectively. CYP2C19 genotypes *1/*1, *1/*2, *1/*3, *2/*2, *2/*3 and *3/*3 frequencies were 84%, 14%, 0.0%, 2.0%, and 0.0%, respectively.CONCLUTION: The result of the present study shows that the two inactive alleles of CYP2C19 accounted for 9.0% of CYP2C19 alleles in our sample versus 8.8 - 40.1% reported in other populations. The frequency of alleles was significant. Differences between our sample and African and Eastern Asian populations.

Background: Clopidogrel is a platelet inhibitor drug widely used in patients undergoing percutaneous coronary intervention (PCI) for the prevention of stent thrombosis. Genetic variation within CYP2C19 gene causes variable clopidogrel response. The FDA has recommended CYP2C19 genotyping in the patients taking clopidogrel, especially in the population with high prevalence rates of CYP2C19 *2 and *3 alleles. Objectives: The aim of this study was to determine the prevalence of CYP2C19 gene polymorphisms in the population received Drug-Eluting Stents following PCI in the southwest of Iran. Methods: This cross-sectional study was conducted on 102 patients undergoing PCI. Demographic characteristics and risk factors of patients were collected using a questionnaire and CYP2C19 genotyping was carried out by PCR-RFLP. Then CYP2C19 allele and genotype frequencies were determined and analyzed using  2 test. Results: Data analysis showed that the frequencies of CYP2C19*1, CYP2C19*2, and CYP2C19*3 allele were 79. 4%, 15. 2%, and 5. 4%, respectively. The frequency of CYP2C19*1/*1 genotype was 60. 8%. Moreover, CYP2C19*1/*2, CYP2C19*1/*3, CYP2C19*2/*3 heterozygote genotypes were shown in 28. 4%, 8. 8%, and 2. 0% of the subjects, respectively. None of the patients had CYP2C19*2/*2 or CYP2C19*3/*3 genotypes. Conclusions: The results of this study showed a high prevalence of CYP2C19*2 polymorphism in the population lived in the southwest of Iran. The frequency of CYP2C19*1/*2 genotype is compatible with the majority of the Iranian population and more similar to Caucasian populations.

Background: There are different clinical responses to omeprazole treatment in Iranian patients with gastroesophageal reflux disease. Omeprazole is metabolized in the liver by the cytochrome p450 2c19 (CYP2C19) enzyme. Two common polymorphisms of the CYP2C19 gene affect CYP2C19 enzyme activity. We investigated the effect of CYP2C19 gene polymorphisms on the clinical response to treatment with omeprazole in Iranian patients with erosive reflux esophagitis.Methods: Eighty-two Iranian patients with reflux esophagitis were enrolled in the study and underwent treatment with omeprazole at 40 mg daily for 4 weeks. A 2 mL sample of venous blood was obtained from each subject. CYP2C19 genetic polymorphisms were detected using the PCR-RFLP method. The patients were grouped into homo-extensive metabolizers and hetero-extensive metabolizers based on their CYP2C19 polymorphism. The grade of esophagitis was determined via endoscopy. The symptoms score was assessed at the beginning of treatment. Results: Our results showed that the rate of complete clinical response to treatment with omeprazole was 95% in the hetero-extensive metabolizers group, which was higher than in the homo-extensive metabolizers group (P<0.001). Conclusion: CYP2C19 polymorphism influences the therapeutic efficacy of omeprazole in the treatment of Iranian patients with erosive reflux esophagitis. The clinical response and endoscopic healing of esophagitis are both affected by CYP2C19 genotype condition.