جستجوی مقالات مرتبط با کلیدواژه "vkorc1" در نشریات گروه "پزشکی"

Warfarin, a commonly prescribed anticoagulant with a narrow therapeutic index, poses challenges in determining the appropriate dosage due to genetic variations among individuals. Incorrect dosing of warfarin can lead to catastrophic adverse events. Observational studies have shown that single nucleotide polymorphisms (SNPs) in the CYP2C9 and VKORC1 genes significantly influence warfarin dose requirements. This study aimed to examine the impact of various genotypes on warfarin dose requirements among Iranian patients.

Blood samples were collected from 117 patients and stored in tubes containing EDTA. DNA was extracted, and the different alleles and genotypes of the studied SNPs were identified using the PCR-RFLP technique.

Among the 117 patients, no significant differences were observed in the mean daily warfarin dose requirement among the genotypes of the CYP2C93 (1075A>C) polymorphism. However, significant differences were found among the genotypes of CYP2C92 (430C>T). Furthermore, the mean daily warfarin dose requirements varied significantly among the wild-type, heterozygous, and mutant genotypes for two VKORC1 polymorphisms: VKORC1 (1173C>T) and VKORC1 (1639G>A).

Our findings demonstrate that CYP2C9 and VKORC1 polymorphisms significantly affect warfarin maintenance dose requirements in Iranian patients. This information can improve the prediction of appropriate warfarin dosages and reduce the risk of over-anticoagulation or under-anticoagulation.

Warfarin is the most widely used oral anticoagulant for the prevention and treatment of thromboembolic disorders. Because of narrow therapeutic index and various genetic and non-genetic factors that influence the disposition of the drug, its dose undergoes a great variability. The aim of this study was to determine the allelic variants of CYP2C9 and VKORC1 genes in Iraqi patients, and to investigate the contribution of genetic on warfarin dose requirements.

A cross sectional study was carried out on a sample of Iraqi patients from Baghdad city who were admitted to Ibn AL-Bitar Specialized Center for cardiac surgery. Blood samples of all patients were collected for both hematological and genetic analysis utilizing standard techniques.

The frequency of CYP2C9*3 allele was 9.4% whereas that of CYP2C9*2 allele was 13.7%. The frequency of (VKORC1-1639G) allele was 58.75% and the frequency of (VKORC1-1639A) allele was 41.25%. Patients’ daily warfarin doses were administered according to their genotype.

It can be concluded that CYP2C9*3 and VKORC1 had significant effect on warfarin dose. New warfarin-dosing algorithm was developed based on CYP2C9*3 and VKORC1genotypes for predicting the required dose of warfarin.

Warfarin is an anticoagulant agent used for many years in treating various clinical conditions such as thromboembolisms in cardiovascular disease. Some patients require different doses of warfarin to reach the therapeutic international normalized ratio ratio. These patients have specific demographic characteristics. Genetic polymorphisms in specific genes have been reported to be an essential factor in response to warfarin. The present study investigated the effect of these polymorphisms of genes on warfarin dose necessities in pediatric of VCORC1 gene in patients.

Ninety-five patients with cardiovascular disease, who were receiving warfarin for at least three months, enrolled in the present cross-sectional study. Their genomic DNA was extracted from their peripheral blood, and the VKORC1 (rs9923231) polymorphism was evaluated by polymerase chain reaction and sequencing.

Among the study population, 48 patients (50.5%) had TC genotype and, 21 (22.1%) and 9 (9.5%) patients have TT and CC genotype, respectively. There was no significant relation between Warfarin dose and VCORC1 genotype in our population (p<0.05). 

The VKORC1 polymorphism (rs9923231) did not significantly affect the warfarin required for cardiovascular disease patients. Further studies evaluating other genes such as CYP2C9 polymorphisms in our population are warranted.

The requirement of varying doses of warfarin for different individuals can be explained by environmental and genetic factors. We evaluated the frequency of vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) variants together with patientdemographic characteristics and investigated their association with warfarin dose requirement with the objective to suggest a warfarin dosing algorithm. In this study, 185 patients with heart valve replacement from West Azerbaijan, Iran were genotyped for VKORC1 (-1639 G>A) and CYP2C9 (*2 and *3 alleles) by PCR-RFLP. Multiple linear regression was performed to create a new warfarin dosing algorithm. The frequency of variants in studied subjects was 12% for CYP2C9 *2, 25.8% for CYP2C9 *3, and 60% for -1639A. The patients who carried the A allele at position -1639 VKORC1 and the variants CYP2C9 *2 and *3 required a significantly lower daily mean warfarin dosage (P = 0.001). Statistical analysis also indicated a significant relationship between the daily maintenance dose of warfarin with age and blood pressure among the studied patients’ cohort (P < 0.001). This study showed that in the heart valve replacement patients considering VKORC1 and CYP2C9 polymorphisms beside demographic characteristics such as age will be helpful in pre-treatment dosing of warfarin which in turn reduces the complications associated with inappropriate warfarin dosing.

Warfarin is a vitamin K antagonist that genetic and non-genetic factors affected on its dose requirement in the patients with cardio vascular disease. The aim of this study was whether the APOE and VKORC1 polymorphisms influence on warfarin dose requirements in the part of Iranian patients. Blood samples were collected from 86 warfarin-treated patients. After extraction of genomic DNA, the VKORC1 (rs9923231) and the APOE (rs429358 and r 7412) polymorphisms were genotyped by PCR-RFLP technique. We found that the Iranian patients carrying genotypes GA or AA of VKORC1 polymorphism tended to receive lower dose of warfarin (p = 0.018). Furthermore, the E3/E3 genotype was observed with the frequency more than 60% in the patients with low dose of warfarin. The BMI and weight also showed a positive correlation with warfarin dose. However, it was not statistically significant (p > 0.05). The results of this study may be useful in defining of warfarin dose algorithms for Iranian patients.

The genetic factors are determinants in required dosage changes of warfarin among which are polymorphisms of CYP2C9 and VKORC1 genes. The present study aimed to determine the allele and genotype frequency of CYP2C9 and VKORC1 genes in Birjand population. This study was conducted on 120 individuals who referred to Imam Reza and Vali-Asr hospitals for PT/INR test. After extracting the genomic DNA, the considered sequences were amplified by PCR, and restriction fragment length polymorphism analysis was done by AvaII and KpnI enzymes to determine allele polymorphisms. Moreover, related sequences of VKORC1, after amplification, were sequenced for determining the genotype. Allelic and genotypic frequencies as well as Hardy-Weinberg equilibrium, observed heterozygosity, expected heterozygosity, and polymorphism information content were calculated by PowerMarker V 3.25 software. Amongst 120 individuals in this study with the mean age of 58.12 ± 12.7 years, 80.8%, 9.1%, and 10% exhibited the alleles of 1, 2, and 3 CYP2C9 gene, respectively. The genotype frequencies of 1/1, 1/2, 2/2, 3/1, 3/2, and 3/3 of this gene were found to be 64.1, 15.8, 0, 17.5, 2.5, and 0 %, respectively. In -1639 G>A region, VKORC1 had normal homozygote genotype (GG) and in 1173 C>T region, heterozygote (CT) with the frequency of 48.7% and 45.9% had the most prevalence. Compared with other populations, there is a considerable difference between the allele frequency of CYP2C9 and VKORC1 genetic variance. Since 35.8% of the selected populations carry an abnormal allele causing sensitivity to warfarin, the specialists at medical centers must be informed about the genotypes of patients before prescribing warfarin.

Warfarin is a common anticoagulant drug that has a narrow therapeutic index; higher dose causes excessive bleeding and lower dose leads to cerebrovascular clotting and stroke in patients. Genetic factors that have been associated with warfarin response are the genes of cytochrome P450 2C9 (CYP2C9), which metabolize the more active S-enantiomer of warfarin, and vitamin K epoxide reductase (VKOR), the target site for warfarin. The present study was conducted to investigate the association between CYP2C9*2, CYP2C9*3 and VKORC1 (-1639 G>A) polymorphisms with warfarin daily dose on 118 Iranian patients under warfarin treatment.
This study is comprised of 118 Iranian patients on warfarin treatment who attended the PT Clinic. Genotyping of CYP2C9*2, CYP2C9*3 and VKORC1 (-1639 G>A) was performed by PCR-RFLP method. Multiple regression model was performed for statistical analyses and P The allelic frequencies of CYP2C9*2 and CYP2C9*3 were 19% and 7%, respectively. Patients with ≥1 CYP2C9 variant allele had a significantly lower mean warfarin daily dose compared with patients with the wild-type genotype. The allelic frequencies of VKORC1 were 14.4%, 57.6% and 27.9% for GG, GA, and AA genotypes, respectively. The mean (SD) warfarin daily dose in patients with the VKORC1 (–1639) GG genotype was significantly higher than GA and AA patients.
CYP2C9*2, CYP2C9*3 and VKORC1 (-1639 G>A) polymorphisms had significant association with warfarin daily dose. Furthermore, the daily warfarin dose was not influenced by age, height, weight and sex.

Warfarin is an effective oral anticoagulant which exert its effect by blocking the utilization of vitamin K. Warfarin therapy requires ongoing monitoring using the international normalized ratio (INR). In this study, effect of modest increase in vitamin K intake from vegetables on INR values was evaluated in warfarin treated patients.
A single-center study involving 24 outpatients (mean age, 62 years) with two last INR in therapeutic range in which INR variations was less than 0.5. Patients were selected based on their VKORC1 1639G→A polymorphism so that 8 patients from each of GG, AA or GA genotypes were recruited. Patients were asked to consume a vegetable mix (including lettuce, peeled cucumber and tomato) containing approximately 100 µg vitamin K (divided in two meals, lunch and dinner) daily for one week when INR response was measured.
Daily consumption of vegetable mix decreased patient’s INR from 2.43±0.51 to 2.08± 0.46 (P Daily increase in vegetable salad containing approximately 100 µg, decreased INR of patients. Therefore, avoiding variation in consumption of foods with even moderate content of vitamin K could help to prevent INR fluctuations in warfarin treated patients.

Managing individual-based anti-coagulant therapy with warfarin is an important goal for bleeding prevention in personalized medicine.. The purpose of the present study was to evaluate the allelic frequency of VKORC1 (C1173T, G1639A) and CYP2C9 (CYP2C9*2 and CYP2C9*3) polymorphic genes with SimpleProbe® real-time PCR as a fast, accurate and easy-to-handle method..Patients and One hundred unrelated patients under warfarin therapy were recruited as the study population. Real-time PCR was performed with SimpleProbe® for single-nucleotide polymorphisms (SNP) detection of CYP2C9 and VKORC1 genes.. The allelic frequencies for VKORC1 C1173T (CC, CT, TT) were 25%, 51% and 24%, respectively and for VKORC1 G1639A (-GG, GA, AA) were 27%, 51% and 22%, respectively. Despite a significant association between allelic polymorphisms in VKORC1 and warfarin dose (P < 0.001), it was not statistically significant for CYP2C9*2 and CYP2C9*3, most probably due to the low rate of CYP2C9*2 and CYP2C9*3 SNPs observed.. SimpleProbe® real-time PCR is a fast and accurate technique qualified to detect VKORC1 and CYP2C9 SNPs. These results encourage taking further steps towards using VKORC1 and CYP2C9 allelic screening to prevent clinical complications due to resistance or sensitivity to warfarin as well as anti-coagulant dose adjustment..