Development of the Genotyping Protocol for the Study of Genetic Polymorphisms of CYP450 2C9 (CYP2C9 * 2, * 3) and VKORC1 1639G> A

  • Safia lazreg EPH de Rélizane, N°3, city 160 ilots, Oules Adda Essenia, Oran 31005, Algéria
  • Habiba fetati EHU d’Oran, service de pharmacovigilance
Keywords: acenocoumarol, genetic polymorphism, VKORC1, CYP2C9, PCR RFLP

Abstract

Two genes are mainly involved in the variability of the response to Acenocoumarol: one encoding the vitamin K epoxide reductase (VKORC1) pharmacological target of AVKs, and the other encoding the cytochrome P450 2C9 (CYP2C9), responsible for the metabolism of coumarin derivatives to inactive metabolites.The objective of our work is to develop a genotyping technique in order to study this genetic polymorphism within the Algerian population.Genotyping is performed by RFLP (restriction fragment length polymorphism) PCR over 4 steps: DNA extraction, amplification, enzymatic digestion and electrophoresis. The FDA has approved that the use of genetic testing may help healthcare professionals better predict steady-state doses of vitamin k antagonists in order to optimize the management of patients treated with this drug.

References

. Tom Schalekamp, et al. Acenocoumarol stabilization is delayed in CYP2C9*3 carriers. Clinical pharmacology and therapeutics.2004; 75(5):394-402.

. T. I. VERHOEF, et al. Long-term anticoagulant effects of the CYP2C9 and VKORC1 genotypes in acenocoumarol users. Journal of Thrombosis and Haemostasis, 10: 606–614 DOI: 10.1111/j.1538-7836.2012.04633.x.

. Jonatan D et al. Several-fold increase in risk of overanticoagulation by CYP2C9 mutations. Clinical Pharmacology & Therapeutics 2005; 78(5):540-50.

. Jose´ Hermida, et al. Differential effects of 2C9*3 and 2C9*2 variants of cytochrome P-450 CYP2C9 on sensitivity to acenocoumarol. Blood, 1 June 2002, Volume 99, Number 11.

. Loes E. Visser et al. The risk of overanticoagulation in patients with cytochrome P450 CYP2C92 or CYP2C93 alleles on acenocoumarol or phenprocoumon. Pharmacogenetics 2004, 14:27–33.

. F. Z. Smires et al. Influence of genetics and non-genetic factors on acenocoumarol maintenance dose requirement in Moroccan patients. Journal of Clinical Pharmacy and Therapeutics, 2012, 37, 594–598

. Allan E. Rettie et al. A case study of acenocoumarol sensitivity and genotypephenotype discordancy explained by combinations of polymorphisms in VKORC1 and CYP2C9. British Journal of Clinical Pharmacology. DOI:10.1111/j.1365-2125.2006.02688.x

. Anupriya Kaur, et al. Cytochrome P450 (CYP2C9 * 2, * 3) & vitamin-K epoxide reductase complex (VKORC1 -1639G

. Laurent Bodin et al. CytochromeP4502C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity. Blood, 1 July 2005, Volume 106, Number 1.

. ElizabethA. Sconce et al. The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood, 1 October 2005. Volume 106, Number 7.

Published
2020-10-24
Section
Articles