Did you know DNA can help with warfarin dosing?
Genetic changes in four genes influence the efficacy of warfarin
It’s flu season. You bring it home and spend the weekend in bed. With painkillers every six hours, an extra dose of ‘Neocitran’ at night, and copious amounts of ginger and lemon tea, you are ready for work by Monday.
Unfortunately for your partner, even with this strict regime of medicine and rest, the flu lingers on for more than a week. The sickness was the same, you both used the same drugs, so why was the outcome so different?
Genes & Drugs
Genetics is one possible answer to this question. Genetic differences control how well a drug is taken up, how fast it is broken down and how fast it gets removed from the body.
This is why different people will respond to the same medication in very different ways. Luckily with painkillers, we have the luxury of experimenting with the dose and the duration. But what happens when a drug overdose could be dangerous?
Warfarin is a drug that is used to treat blood clots, before further complications happen. However with warfarin, the dose has to be near to perfect from the get go. The patient needs to have a high enough dose to protect against life-threatening blood clots, while too much can cause excessive bleeding.
Yet, determining the correct warfarin dose is extremely complicated. On top of factors like age, sex, height, weight and diet that affect the dosage of any medication, the effectiveness of warfarin is also heavily influenced by genetic differences.
Vitamin K1 & Blood Clots
Warfarin acts by blocking the VKORC1 enzyme, which recycles inactive vitamin K1 into its active form. Vitamin K1 promotes blood clotting, and is often used to prevent “blood thinning”.
Genetic changes in the VKORC1 gene decrease enzyme levels. So, patients with these changes need a lower dose of warfarin, to achieve the desired anticoagulant affect.
Variants in three other genes, GGCX, CYP2C9 and CYP4F2, also influence warfarin dosing. The protein encoded by the GGCX gene functions in vitamin K1 production. GGCX variation can decrease vitamin K1 levels, so a low dose of warfarin is sufficient.
CYP2C9 encodes an enzyme that breaks down warfarin. There are several changes in the CYP2C9 gene, and each decrease the enzyme activity. This means warfarin will be broken down slower, so these patients will need less drug.
On the other hand, altered forms of CYP4F2 can increase vitamin K1 levels. People who carry these variants will need a higher than normal warfarin dose to prevent clotting. An online tool is available at WarfarinDosing.org for estimating the therapeutic dose of warfarin that based on each of these genetic differences.
Optimize Your Warfarin Dose With DNA
Warfarin is the most widely used anticoagulant in the world. It is extremely effective when the proper dose is achieved. Yet, even with more than 60 years of research, determining the proper dosage of warfarin continues to be a challenge.
The requirements for properly regulating vitamin K levels through diet, and for avoiding an extensive list of medications that interact with warfarin, add to the complexity of this challenge.
Genetic testing to assist in defining therapeutic doses of warfarin offers one of the safest solutions to this complicated problem. If knowing your genetic differences can make warfarin safer, would you take the DNA Warfarin Sensitivity Test?