Methods and compositions for the assessment of drug response

Abstract

The present invention provides methods for predicting or determining a subject's response to an antiplatelet agent, and methods for determining a subject's suitability to a treatment regime or intervention for a disease associated with platelet aggregation, using analysis of genetic polymorphisms. The present invention also relates to the use of genetic polymorphisms in assessing a subject's response to an antiplatelet agent. Nucleotide probes and primers, kits, and microarrays suitable for such assessment are also provided

We claim: 
     
         1 . A method comprising:
 a) analyzing a sample from a subject with a SNP detection assay to determine that said subject is homozygous for the −806C/T polymorphism in the CYP2C19 gene (CYP2C19*17), thereby generating a homozygous CYP2C19*17 genetic analysis result;   b) inputting said homozygous CYP2C19*17 genetic analysis result into a system, wherein said system comprises:
 i) a computer processor for receiving, processing, and communicating data, 
 ii) a storage component for storing data which contains a reference genetic database of results of at least one genetic analysis of CYP2C19*17 homozygosity with respect to response to a thienopyridine anti-platelet agent, and 
 iii) a computer program, embedded within said computer processor, which is configured to process said homozygous CYP2C19*17 genetic analysis result in the context of said reference database to determine, as an outcome, that said subject should receive decreased loading and/or maintenance dosages of said thienopyridine anti-platelet agent compared to CYP2C19 wild-type dosage levels; 
   c) processing said homozygous CYP2C19*17 genetic analysis result with said computer program in the context of said reference database to generate said outcome; and   d) communicating said outcome from said computer program, wherein said outcome indicates that said subject should receive decreased loading and/or maintenance dosages of said thienopyridine anti-platlet agent compared to CYP2C19 wild-type dosage levels.   
     
     
         2 . The method of  claim 1 , further comprising the step of analyzing said sample with a SNP detection assay for the presence or absence of the 636 G>A polymorphism in said CYP2C19 gene (CYP2C19*3 polymorphism). 
     
     
         3 . The method of  claim 2 , further comprising the step of analyzing said sample with a SNP detection assay for the presence or absence of the 19154G/A polymorphism in said CYP2C19 gene (CYP2C19*2 polymorphism). 
     
     
         4 . The method of  claim 1 , wherein said thienopyridine anti-platelet agent comprises clopidogrel. 
     
     
         5 . The method of  claim 1 , wherein said thienopyridine anti-platelet agent comprises prasugrel. 
     
     
         6 . A method comprising:
 a) analyzing a sample from a subject with a SNP detection assay to determine that said subject is homozygous for the −806C/T polymorphism in the CYP2C19 gene (CYP2C19*17), thereby generating a homozygous CYP2C19*17 genetic analysis result; and   b) processing said homozygous CYP2C19*17 genetic analysis result with a computer system to generate an outcome that indicates that said subject should receive decreased loading and/or maintenance dosages of thienopyridine anti-platelet agent compared to CYP2C19 wild-type dosage levels.   
     
     
         7 . The method of  claim 4 , further comprising the step of analyzing said sample with a SNP detection assay for the presence or absence of the 636 G>A polymorphism in said CYP2C19 gene (CYP2C19*3 polymorphism). 
     
     
         8 . The method of  claim 5 , further comprising the step of analyzing said sample with a SNP detection assay for the presence or absence of the 19154G/A polymorphism in said CYP2C19 gene (CYP2C19*2 polymorphism). 
     
     
         9 . The method of  claim 4 , wherein said thienopyridine antiplatelet agent comprises clopidogrel. 
     
     
         10 . The method of  claim 4 , wherein said thienopyridine antiplatelet agent comprises prasugrel. 
     
     
         11 . A method comprising:
 a) providing a subject that is homozygous for the −806C/T polymorphism in the CYP2C19 gene (CYP2C19*17), and   b) administering to said subject decreased loading and/or maintenance dosages of an thienopyridine anti-platelet agent compared to CYP2C19 wild-type dosage levels.   
     
     
         12 . The method of  claim 11 , wherein said thienopyridine anti-platelet agent comprises clopidogrel. 
     
     
         13 . The method of  claim 11 , wherein said thienopyridine anti-platelet agent comprises prasugrel.