Warfarin Sensitivity and the VKORC1 Gene
Warfarin, a drug used to prevent the formation or growth of blood clots, is commonly prescribed to patients who have experienced irregular heartbeat, a heart attack or heart valve replacement surgery. Despite its established use, dosage can be difficult to determine and is critical since abnormal bleeding can occur if the dosage is too high.
Complicating the matter, racial differences in response to warfarin must be considered; compared to people of European ancestry, people of Chinese origin are more sensitive, and African Americans less sensitive. A number of genes have been identified that appear to account for variation in warfarin sensitivity:
- Vitamin K epoxide reductase complex 1 (VKORC1) that influences transcriptional regulation
- Hepatic microsomal enzyme P450 2C9 (Cyp2C9)
- Coagulation factors II and VII
In a recent PLoS Medicine publication, a case-control study found that the C1173T polymorphism in intron 1 of the VKORC1 gene has a significant effect on dose requirement and occurrence of severe bleeding in subjects treated with the long-acting coumarin phenprocoumon or short-acting acenocoumarol. Carriers of the T allele appear to be at greater risk of bleeding and are more sensitive to coumarin.
Results such as these remind us that personalized medicine, which takes into account our unique genetic make-up, will help to define medications and dosages that are just right for us.
PLoS Medicine, 2(10): e342
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POSTED IN: General Genetics and Health
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2 opinions for Warfarin Sensitivity and the VKORC1 Gene
Genetics and Health » New Genetics and Health Poll: How much for your DNA sequence?
Jul 27, 2006 at 4:43 am
[…] My thinking on this might be a little counterintuitive. At this point in time, our understanding of the impact specific genes have on our overall health is somewhat limited. We know that certain genes increase our risk of cancer, like BRCA or HNPCC, and that other genes might affect how we metabolize certain drugs. But beyond that, the majority of our DNA sequence doesn’t really tell us much yet. So I figure knowing our genomic sequence isn’t worth much now and prices (if it weren’t limited by technology) would be depressed. […]
Genetics and Health » Warfarin Sensitivity DNA Test
Nov 15, 2006 at 11:47 pm
[…] Kimball Genetics, Inc. has launched the Warfarin Sensitivity DNA Test for routine clinical use early next year. It tests for variations in the CYP2C9 and VKORC1 genes which play a role in determining a person’s sensitivity to warfarin via metabolism and anticoagulation processes, respectively. Warfarin (brand name Coumadin) prevents blood clots is typically prescribed for patients who are experiencing irregular heartbeat or those who’ve had a heart attack or heart valve replace surgery. The Warfarin Sensitivity DNA Test that Kimball offers informs the prescriber about the presence of genetic risk factors for overanticoagulation and should help achieve the correct maintenance dose faster. It is also likely to increase the safety and efficacy of warfarin treatment. The DNA test identifies patients who are sensitive to warfarin and who therefore: 1) require a lower dose to achieve a target INR, 2) may be at an increased risk for bleeding complications, and 3) without the DNA test, would require a longer period of time to achieve stable warfarin dosing. […]
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