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 approximately 95% 
of Jews, approximately 84% of Druze and approximately 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.