CYP2C9*8 Alleles Correlate With Decreased Warfarin Metabolism And Increased Warfarin Sensitivity
The present disclosure is related to a method of identifying a subject with increased sensitivity to warfarin. The method includes identifying a CYP2C9*8 polymorphism in the subject, wherein the presence of said polymorphism is indicative of a patient with increased sensitivity to warfarin relative to a subject having the corresponding wild-type allele.
1 . A method of administering warfarin or a warfarin derivative to a subject in need thereof, comprising:
determining whether a subject possesses a CYP2C9*8 allele and, if that subject possesses said allele,
administering an amount of warfarin or warfarin derivative more appropriate than would be administered to a homozygous wild type patient not bearing said allele.
2 . The method of claim 1 wherein said amount is a lower amount.
3 . The method of claim 1 wherein said subject is African-American, black African, or of black African descent.
4 . The method of claim 1 wherein said homozygous wild type is *1/*1.
5 . The method of claim 1 wherein said subject is homozygous for said allele.
6 . The method of claim 1 wherein said subject is heterozygous for said allele.
7 . The method of claim 2 wherein the genotype of said subject is *5/*8.
8 . The method of claim 2 wherein the genotype of said subject is *8/*11.
9 . The method of claim 1 wherein the genotype of said subject is *8 combined with one or more other alleles associated with reduced metabolism of warfarin.
10 . The method of claim 9 wherein said some one or more other alleles associated with reduced metabolism of warfarin is selected from the group consisting of *2, *3, *5, *6 and *11.
11 . The method of claim 9 wherein the *8 genotype is combined with each of the genotypes for *2, *3, *5, *6, and *11.
12 . The method of claim 9 wherein the *8 genotype is combined with each of the genotypes for *5, *6, and *11.
13 . The method of claim 1 wherein said administering step comprises administering between about 55% and 85% of the warfarin dose that would be administered to a homozygous wild type patient.
14 . The method of claim 1 wherein said administering step comprises administering to said subject between about 25 mg/week and 40 mg/week.
15 . A warfarin dosing algorithm, said warfarin dosing algorithm comprising one more mathematical operations that consider CYP2C9*8 genotype in calculating, predicting, and/or prescribing warfarin dosage to a patient, and wherein said calculating, predicting, and/or prescribing comprises a lower amount of warfarin relative to a homozygous wild type CYP2C9 genotype.
16 . A method of identifying a subject with increased sensitivity to warfarin comprising:
identifying a CYP2C9*8 polymorphism in said subject, wherein the presence of said polymorphism is indicative of a patient with increased sensitivity to warfarin relative to a subject having the corresponding wild-type allele.
17 . The method of claim 16 , wherein said identifying comprises detecting the polymorphism in the DNA of said subject.
18 . The method of claim 16 , wherein said identifying comprises detecting the polymorphism in the CYP2C9 gene product.