Distribution of CYP2C9 and VKORC1 risk alleles for warfarin sensitivity and resistance in the Israeli population

Edna Efrati, Hela Elkin, Eli Sprecher, Norberto Krivoy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Purpose: This study was designed to delineate the relative frequency of CYP2C9 and VKORC1 polymorphisms known to affect warfarin response in the highly heterogeneous Israeli population. Methods: Frequencies of CYP2C9 allelic variants CYP2C9*2, CYP2C9*3 and of VKORC1 single nucleotide polymorphisms (snps)-1639G>A and D36Y were determined in genomic DNA of 438 healthy unrelated Israeli volunteers of Jewish, Druze and Arab Moslem descent, using allele specific PCR-RFLP. Genotyping results obtained were confirmed by probe free High Resolution Melt (HRM) Technology. Results: Arab Moslems had a higher frequency of warfarin "sensitive" CYP2C9*2, CYP2C9*3 and VKROC1-1639G>A alleles (0.21, 0.07 and 0.58, respectively) than both Jews (0.13, 0.11 and 0.57, respectively) and Druze (0.12, 0.06 and 0.53, respectively). Statistically significant differences were found in CYP2C9*2 between Druze and Moslems (p=0.01) and between Jews and Moslems (p=0.016) and in CYP2C9*3 between Druze and Jews (p=0.0086). VKORC1(-1639G>A) was the major gene polymorphism associated with warfarin sensitivity in all 3 subpopulations. In contrast, the warfarin "resistant" VKORC1 D36Y allele was very rare in the Israeli population (0-0.015). The results presented demonstrate that allelic variants in CYP2C9 and VKORC1 are very common in Israel with ~95% of Jews, ~84% of Druze and ~91% of Arab Moslems manifesting at least one known warfarin "sensitive" or "resistant" allele. Conclusions: Individualized genotype based warfarin therapy is highly relevant in the Israeli population due to the high incidence of genetic variations associated with warfarin sensitivity in all 3 non-mixing subpopulations tested.

Original languageEnglish
Pages (from-to)190-193
Number of pages4
JournalCurrent Drug Safety
Issue number3
StatePublished - 2010
Externally publishedYes


  • CYP2C9
  • HRM
  • Pharmacogenetics
  • Single nucleotide polymorphism
  • VKORC1
  • Warfarin


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