Open AccessAnalysis of CYP 2C9*2 , CYP 2C9*3 and VKORC 1 ‐1639 G>A polymorphisms in a population from S outh‐ E astern E urope
Author(s) -
Buzoianu Anca D.,
Trifa Adrian P.,
Mureşanu Dafin F.,
Crişan Sorin
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2012.01606.x
Subject(s) - cyp2c9 , genotype , biology , genetics , allele , population , allele frequency , medicine , gene , environmental health
The CYP 2C9 enzyme metabolizes a wide range of relevant drugs, among which are oral anticoagulants. VKORC 1 is the pharmacodynamic target of the oral anticoagulants. The genetic polymorphisms CYP 2C9*2 , CYP 2C9*3 and VKORC 1 ‐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 CYP 2C9*2 , CYP 2C9*3 and VKORC 1 ‐1639 G>A polymorphisms using the PCR ‐ RFLP technique. Sixty‐two individuals (18.7%) were heterozygous for CYP 2C9*2 , whereas 47 individuals (14.1%) were heterozygous for CYP 2C9*3 . Fourteen individuals (4.2%) had a CYP 2C9*2 homozygous, CYP 2C9*3 homozygous or CYP 2C9*2 / CYP 2C9*3 compound heterozygous genotype. These individuals are predicted to have the lowest CYP 2C9 enzymatic activity. The allele frequencies of the CYP 2C9*2 and CYP 2C9*3 polymorphisms were 11.3% and 9.3% respectively. For the VKORC 1 ‐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 CYP 2C9*2 , CYP 2C9*3 and VKORC 1 ‐1639 G>A polymorphisms observed in our cohort is in accordance with other C aucasian populations. A large number of Romanians are expected to harbour at least one CYP 2C9 variant allele and/or one VKORC 1 ‐1639 G>A allele. This frequency has major implications in the pharmacogenomics of oral anticoagulants in R omanians.