Genetic polymorphisms associated with cardiovascular disorders and drug response, methods of detection and uses thereof

Abstract

The present invention is based on the discovery of genetic polymorphisms that are associated with cardiovascular disorders, particularly acute coronary events such as myocardial infarction and stroke, and genetic polymorphisms that are associated with responsiveness of an individual having a cardiovascular disorder to treatment of the disorder with statin. In particular, the present invention relates to nucleic acid molecules containing the polymorphisms, variant proteins encoded by such nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and proteins, and methods of using the nucleic acid and proteins as well as methods of using reagents for their detection.

1 . A test kit for detecting a single nucleotide polymorphism (SNP) in gene KIF6 in a test sample, said test kit comprising a container containing a SNP detection reagent which detects the presence of G or A at position 101 of SEQ ID NO: 263 or C or T at position 101 of its complement. 
     
     
         2 . The test kit of  claim 1 , wherein said container is enclosed in a package. 
     
     
         3 . The test kit of  claim 2 , wherein said SNP detection reagent comprises at least one primer. 
     
     
         4 . The test kit of  claim 3 , wherein said primer is an allele-specific primer. 
     
     
         5 . The test kit of  claim 3 , wherein said primer is detectably labeled. 
     
     
         6 . The test kit of  claim 3 , further comprising a container enclosed in said package containing an enzyme. 
     
     
         7 . The test kit of  claim 6 , wherein said enzyme is a polymerase enzyme. 
     
     
         8 . The test kit of  claim 7 , wherein said polymerase enzyme is thermostable. 
     
     
         9 . The test kit of  claim 6 , further comprising a container enclosed in said package containing deoxynucleotide triphosphates (dNTPs). 
     
     
         10 . The test kit of  claim 6 , further comprising a container enclosed in said package containing dideoxynucleotide triphosphates (ddNTPs). 
     
     
         11 . The test kit of  claim 2 , wherein said SNP detection reagent comprises at least one probe. 
     
     
         12 . The test kit of  claim 11 , wherein said probe is an allele-specific probe. 
     
     
         13 . The test kit of  claim 11 , wherein said probe is detectably labeled. 
     
     
         14 . The test kit of  claim 11 , further comprising a container enclosed in said package containing an enzyme. 
     
     
         15 . The test kit of  claim 14 , wherein said enzyme is a ligase enzyme. 
     
     
         16 . The test kit of  claim 15 , wherein said ligase enzyme is thermostable. 
     
     
         17 . The test kit of  claim 2 , further comprising a container enclosed in said package containing a buffer. 
     
     
         18 . The test kit of  claim 2 , further comprising a container enclosed in said package containing a control nucleic acid. 
     
     
         19 . The test kit of  claim 18 , wherein said control nucleic acid is a positive control. 
     
     
         20 . The test kit of  claim 18 , wherein said control nucleic acid is a negative control. 
     
     
         21 . The test kit of  claim 3 , further comprising a container enclosed in said package containing a reagent for extracting nucleic acid from said test sample. 
     
     
         22 . The test kit of  claim 3 , further comprising instructions for using said test kit which instruct that the presence of said G or said C indicates an increased risk for myocardial infarction, or the presence of said A or said T indicates no said increased risk. 
     
     
         23 . The test kit of  claim 3 , further comprising instructions for using said test kit which instruct that the presence of said G or said C indicates a reduction of likelihood of developing myocardial infarction following treatment with an HMG-CoA reductase inhibitor.