Evaluation of a reverse-hybridization StripAssay for the detection of genetic polymorphisms leading to acenocoumarol sensitivity
| Autor: | Efrosyni Merkouri, Elisabeth Grouzi, Argyri Gialeraki, Anthi Travlou, Christos Markatos, Marianna Politou |
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| Rok vydání: | 2009 |
| Předmět: |
Molecular Sequence Data
Single-nucleotide polymorphism Polymorphism Single Nucleotide DNA sequencing Mixed Function Oxygenases Vitamin K Epoxide Reductases Genetics medicine Humans Molecular Biology CYP2C9 Cytochrome P-450 CYP2C9 Acenocoumarol Base Sequence biology Nucleic Acid Hybridization Cytochrome P450 Heterozygote advantage Sequence Analysis DNA General Medicine Molecular biology biology.protein Vitamin K epoxide reductase Aryl Hydrocarbon Hydroxylases Reagent Kits Diagnostic Restriction fragment length polymorphism Polymorphism Restriction Fragment Length medicine.drug |
| Zdroj: | Molecular Biology Reports. 37:1693-1697 |
| ISSN: | 1573-4978 0301-4851 |
| DOI: | 10.1007/s11033-009-9587-2 |
| Popis: | Acenocoumarol is mainly catabolized by CYP2C9 isoform of cytochrome P450 (CYP) liver complex and exerts its anticoagulant effect through the inhibition of Vitamin K Epoxide Reductase (VKOR). The most important genetic polymorphisms which lead to an impaired enzymatic activity and therefore predispose to acenocoumarol sensitivity, are considered to be CYP2C9*2 (Arg144Cys), CYP2C9*3 (Ile359Leu) and VKORC1-1639G>A, respectively. In this study we compared the results of the PGXThrombo StripAssay kit (ViennaLab Diagnostics,Vienna, Austria) with direct DNA sequencing and in house Restriction Fragment Length Polymorphisms (RFLP) for the detection of the aforementioned Single Nucleotide Polymorphisms (SNPs). The reverse hybridization StripAssay was found to be equally effective with RFLP and direct DNA sequencing for the detection of CYP2C9*2 and CYP2C9*3 polymorphisms, respectively. The comparison of the RFLP reference method with the reverse hybridization StripAssay for the detection of VKORC1-1639 G>A polymorphism showed that the reverse hybridization StripAsssay might misclassify some A/A homozygotes as heterozygotes. Optimization of the hybridization procedures may eliminate the extra low signal band observed in some samples at the reverse hybridization StripAssay and improve its diagnostic value. |
| Databáze: | OpenAIRE |
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