Dataset Information

Analysis of CYP2C92, CYP2C93 and VKORC1 -1639 G>A polymorphisms in a population from South-Eastern Europe.

ABSTRACT: The CYP2C9 enzyme metabolizes a wide range of relevant drugs, among which are oral anticoagulants. VKORC1 is the pharmacodynamic target of the oral anticoagulants. The genetic polymorphisms CYP2C9*2, CYP2C9*3 and VKORC1 -1639 G>A are the major determinants of the inter-individual variability in the dosage requirements of oral anticoagulants. This study provides a first evaluation of these 3 polymorphisms in a Romanian population. A total of 332 Romanian individuals were genotyped for the CYP2C9*2, CYP2C9*3 and VKORC1 -1639 G>A polymorphisms using the PCR-RFLP technique. Sixty-two individuals (18.7%) were heterozygous for CYP2C9*2, whereas 47 individuals (14.1%) were heterozygous for CYP2C9*3. Fourteen individuals (4.2%) had a CYP2C9*2 homozygous, CYP2C9*3 homozygous or CYP2C9*2/CYP2C9*3 compound heterozygous genotype. These individuals are predicted to have the lowest CYP2C9 enzymatic activity. The allele frequencies of the CYP2C9*2 and CYP2C9*3 polymorphisms were 11.3% and 9.3% respectively. For the VKORC1 -1639 G>A polymorphism, there were 170 heterozygotes (51.2%) and 55 (16.6%) homozygotes for the A allele. The frequency of the A allele was 42.2%. Overall, the distribution of the CYP2C9*2, CYP2C9*3 and VKORC1 -1639 G>A polymorphisms observed in our cohort is in accordance with other Caucasian populations. A large number of Romanians are expected to harbour at least one CYP2C9 variant allele and/or one VKORC1 -1639 G>A allele. This frequency has major implications in the pharmacogenomics of oral anticoagulants in Romanians.

SUBMITTER: Buzoianu AD

PROVIDER: S-EPMC4393720 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Analysis of CYP2C92, CYP2C93 and VKORC1 -1639 G>A polymorphisms in a population from South-Eastern Europe.

Buzoianu Anca D AD Trifa Adrian P AP Mureşanu Dafin F DF Crişan Sorin S

Journal of cellular and molecular medicine 20121201 12

The CYP2C9 enzyme metabolizes a wide range of relevant drugs, among which are oral anticoagulants. VKORC1 is the pharmacodynamic target of the oral anticoagulants. The genetic polymorphisms CYP2C9*2, CYP2C9*3 and VKORC1 -1639 G>A are the major determinants of the inter-individual variability in the dosage requirements of oral anticoagulants. This study provides a first evaluation of these 3 polymorphisms in a Romanian population. A total of 332 Romanian individuals were genotyped for the CYP2C9* ...[more]

PMID: 22863573

Similar Datasets

Project description:BackgroundWarfarin is the most recommended oral anticoagulant after artificial mechanical valve replacement therapy. However, the narrow therapeutic window and varying safety and efficacy in individuals make dose determination difficult. It may cause adverse events such as hemorrhage or thromboembolism. Therefore, advanced algorithms are urgently required for the use of warfarin.ObjectiveTo establish a warfarin dose model for patients after prosthetic mechanical valve replacement in southern China in combination with clinical and genetic variables, and to improve the accuracy and ideal prediction percentage of the model.MethodsClinical data of 476 patients were tracked and recorded in detail. The gene polymorphisms of VKORC1 (rs9923231, rs9934438, rs7196161, and rs7294), CYP2C9 (rs1057910), CYP1A2 (rs2069514), GGCX (rs699664), and UGT1A1 (rs887829) were determined using Sanger sequencing. Multiple linear regressions were used to analyze the gene polymorphisms and the contribution of clinical data variables; the variables that caused multicollinearity were screened stepwise and excluded to establish an algorithm model for predicting the daily maintenance dose of warfarin. The ideal predicted percentage was used to test clinical effectiveness.ResultsA total of 395 patients were included. Univariate linear regression analysis suggested that CYP1A2 (rs2069514) and UGT1A1 (rs887829) were not associated with the daily maintenance dose of warfarin. The new algorithm model established based on multiple linear regression was as follows: Y = 1.081 - 0.011 (age) + 1.532 (body surface area)-0.807 (rs9923231 AA) + 1.788 (rs9923231 GG) + 0.530 (rs1057910 AA)-1.061 (rs1057910 AG)-0.321 (rs699664 AA). The model accounted for 61.7% of individualized medication differences, with an ideal prediction percentage of 69%.ConclusionGGCX (rs699664) may be a potential predictor of warfarin dose, and our newly established model is expected to guide the individualized use of warfarin in clinical practice in southern China.

Dataset Information

Analysis of CYP2C92, CYP2C93 and VKORC1 -1639 G>A polymorphisms in a population from South-Eastern Europe.

Publications

Analysis of CYP2C92, CYP2C93 and VKORC1 -1639 G>A polymorphisms in a population from South-Eastern Europe.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Analysis of CYP2C9*2, CYP2C9*3 and VKORC1 -1639 G>A polymorphisms in a population from South-Eastern Europe.

Publications

Analysis of CYP2C9*2, CYP2C9*3 and VKORC1 -1639 G>A polymorphisms in a population from South-Eastern Europe.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Analysis of CYP2C92, CYP2C93 and VKORC1 -1639 G>A polymorphisms in a population from South-Eastern Europe.

Analysis of CYP2C92, CYP2C93 and VKORC1 -1639 G>A polymorphisms in a population from South-Eastern Europe.