Warfarin (sold under brand names Coumadin, Jantoven, Marevan, and Waran) is a commonly prescribed anticoagulant drug used primarily to prevent thrombosis and embolism (abnormal formation and migration of blood clots). It is also notable in that relatively common SNPs in the VKORC1 and CYP2C9 genes influence the best dose for any given individual. A site aiding physicians in calculating warfarin dosages can be found at warfarindosing.org according to this press release.
A 2007 FDA action stipulates that the possibility of genetic testing for SNPs in the CYP2C9 and VKORC1 genes be included on the label for the medicine known as warfarin (trade name Coumadin). Some medical centers offer genetic screening tests for patients who have conditions that are often treated with simvastatin, clopidogrel, or warfarin. [1]
The SNPs in CYP2C9 include rs1057910 and rs1799853; the SNP in VKORC1 is rs8050894. Note however that tight linkage between several VKORC1 SNPs exist, so for example, the rs9923231 SNP (also known as -1639G>A) may be equivalent to rs8050894 for testing purposes.
These snps are known to influence the correct dosage:
- rs216013
- rs1057910
- rs1799853
- rs8050894
- rs9923231
- rs11676382
- rs28940302
- rs28940303
- rs28940304
- rs28940305
Mutations in the VKORC1 gene are known to cause warfarin resistance (as well as multiple coagulation factor deficiency type 2) [PMID 14765194]. At the amino acid (protein) level, these include mutations in residues 29, 45, 58, 98, and 128. These variations have rs#'s in dbSNP:
- rs104894539 Val29Leu
- rs104894540 Val45Ala
- rs104894541 Arg58Gly
- rs104894542 Leu128Arg
For a more detailed list of non-synonymous SNPs causing warfarin resistance, see [PMID 24287886] which further discusses the current state of SNP entries associated with warfarin dosage phenotypes in online databases (including human genome sequencing databases) as of Nov 2013.
Indian, Chinese and Malay patients need different dosages of the commonly used anti-clotting drug warfarin [2]
[PMID 17764537] rs11676382 was associated with a warfarin maintenance dose across all analysis methods. the effects of GGCX are potentially population/treatment-dependent and will not have broad utility for determining warfarin dosing.
[PMID 18535201] Concludes that SNPs within the VKORC1 and CYP2C9 genes are likely to be the only common SNPs with large effects on warfarin dose.
Promethease checks warfarin dosing via
and
