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Blood clot diagram

Diagram of a thrombus, or colloquially a blood clot.

About Edit

Warfarin (also known by the brand names Coumadin, Jantoven, Marevan, Uniwarfin) Sensitivity Genotyping is the process by which a given individual is screened for their ability to respond to the anticoagulant Warfarin. Warfarin is a prescription drug that helps to prevent blood clots from forming. Blood clots can block blood flow and cause very serious health crises such as heart attack or stroke.

Numerous genetic and non-genetic factors influence how the body responds to Warfarin. Warfarin sensitivity genotyping takes into account only the genetic variants that play a role in the body's sensitivity to the drug. However, genetic data alone is not sufficient to determine optimal dosage. A number of factors including age, sex, weight, diet, and a blood test called INR are all taken into account by physicians when attempting to determine the proper dosage for a given patient. The genetic variants may be a considered by a doctor in addition to the non-genetic factors, most notably when attempting to determine an initial dosage of Warfarin.

Warfarin Sensitivity and Genetics Edit

Warfarin exerts its anti-clotting effects by inhibiting a gene called VKORC1 which is involved in vitamin K recycling. Vitamin K is needed for blood clots to form. This lowers vitamin K levels in the body, resulting in less clotting due to the inactivation of proteins involved in clotting that require vitamin K to function.

23andMe Warfarin (Coumadin®) Sensitivity Genotyping results are based on established research for 3 reported markers following July 28th, 2014. Two of the variants correspond with the *2 and *3 of a gene called CYP2C9 which determines how quickly Warfarin is broken down in the body. The third variant is in a gene called VKORC1, which controls vitamin K levels in the blood. Knowledge of the combinations of these variants can be useful for physicians when seeking to determine an initial dose of Warfarin that can later be adjusted to a optimal level. More research is needed to determine how genetics may or may not improve warfarin treatment.

John Burke's Warfarin Sensitivity Edit

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Genotype for Dr. John Burke in the CYP2C9 and VKORC1 genes:

According to his genetics, John Burke is expected to exhibit a typical sensitivity to Warfarin. Professor Burke's genome contains the SNP rs1799853, meaning he carries the "CC" genotype, that is, the gene combinationCYP2C9*1/*1, VKORC1-1639/3673 AG. Versions of the CYP2C9 gene known as *2 and *3 can slow down the body's ability to break down Warfarin, causing the drug to stay in the body longer. This means that the patient will require a lower dose to begin with. Professor Burke's genome is CC which means he has has two copies of the normally functioning CYP2C9*1 gene. Some people have a version of the VKORC1 gene that reduces its function even in the absence of warfarin, meaning they will require less of the drug in order for it to exert it's function. This version is indicated by a "T" in the genome at the rs1057910 SNP. Professor Burke's genome does not have a T at that locus, meaning he does not produce the version of the VKORC1 that reduces its function on it's own.

References Edit

1. "Warfarin." In Wikipedia. Retrieved September 15, 2014, from [[1]]

2. "23andMe - Genetic Testing for Ancestry." Warfarin Overview. 23andMe, 28 July 2014. Web. 15 Sept. 2014. https://www.23andme.com/you/journal/warfarin/techreport/

3. International Warfarin Pharmacogenetics Consortium. "Estimation of the warfarin dose with clinical and pharmacogenetic data." The New England journal of medicine 360.8 (2009): 753. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722908/

4. "23andMe - Genetic Testing for Ancestry." Health and Traits: Drug Response. 23andMe, n.d. Web. 15 Sept. 2014. https://www.23andme.com/you/journal/warfarin/techreport/