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Warfarin Sensitivity Genotyping



Genotype-guided Warfarin Dosing9

Slide 19

August 2008

A study that is being performed by Brian Gage and colleagues at the Washington University in St. Louis has been trying to ascertain the optimal dose for individuals based upon the two genotypes for the CYP2C9 gene and the VKORC1 promoter. They found that most individuals as indicated earlier would be treated successfully utilizing standard doses as predicted from non-genetic factors.

For example individuals who were heterozygous have one copy of the A and one copy of the G allele in the promoter VKORC1 and have no polymorphisms in the CYP2C9 gene would require the standard dose. Individuals who have two copies of the G allele in the VKORC1 gene and so would make much more VKORC1 protein require a slightly higher dose, for example those who might require between 5 and 7 milligrams of warfarin per day. And those who have the two copies of the VKORC1 A allele required substantially lower dose 73% that which was calculated from non-genetic factors.

What is most important is to realize that individuals who have polymorphisms in both genes will require significantly lower doses than calculated based upon age, weight and height. In individuals who are homozygous or who have two copies of the *3 CYP2C9 alleles and who are also homozygous having two copies of the 1639 A allele in the VKORC1 promoter, they are going to require significantly lower doses and these individuals should be monitored carefully for changes in the INR.

Genotype-guided Warfarin Dosing9

 


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