Edna Efrati1, Hela Elkin, Eli Sprecher, Norberto Krivoy. 1. Center for Translational Genetics, B. Rappaport Institute for Research in Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology and Rambam Health Care Campus, Haifa, Israel.
Abstract
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.
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" VKORC1D36Y 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.
Authors: Mohamed Hossam A Shahin; Larisa H Cavallari; Minoli A Perera; Sherief I Khalifa; Anne Misher; Taimour Langaee; Shitalben Patel; Kimberly Perry; David O Meltzer; Howard L McLeod; Julie A Johnson Journal: Thromb Haemost Date: 2013-03-21 Impact factor: 5.249
Authors: Travis J O'Brien; Arthur F Harralson; Tuyen Tran; Ian Gindoff; Funda E Orkunoglu-Suer; David Frankfurter; Paul Gindoff Journal: Reprod Biol Endocrinol Date: 2014-05-09 Impact factor: 5.211