Genetic polymorphisms associated with stroke, methods of detection and uses thereof

Abstract

The present invention provides compositions and methods based on genetic polymorphisms that are associated with vascular diseases such as stroke. In particular, the present invention relates to genetic polymorphisms that have utility for such uses as predicting disease risk or predicting an individual's response to a treatment such as statins, including groups of polymorphisms that may be used as a signature marker set for such uses, as well as 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 method of determining whether a human has an altered risk for stroke, comprising testing nucleic acid from said human for the presence or absence of a polymorphism selected from the group consisting of the polymorphisms represented by position 101 of any one of the nucleotide sequences of SEQ ID NOS:436-1566 or its complement, wherein the polymorphism indicates an altered risk for stroke. 
     
     
         2 - 3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the altered risk is an increased risk. 
     
     
         5 . The method of  claim 1 , wherein the altered risk is a decreased risk. 
     
     
         6 . The method of  claim 1 , wherein said nucleic acid is a nucleic acid extract from a biological sample from said human. 
     
     
         7 . The method of  claim 6 , wherein said biological sample is blood, saliva, or buccal cells. 
     
     
         8 . The method of  claim 6 , further comprising preparing said nucleic acid extract from said biological sample prior to said testing step. 
     
     
         9 . The method of  claim 8 , further comprising obtaining said biological sample from said human prior to said preparing step. 
     
     
         10 . The method of  claim 1 , wherein said testing step comprises nucleic acid amplification. 
     
     
         11 . The method of  claim 10 , wherein said nucleic acid amplification is carried out by polymerase chain reaction. 
     
     
         12 . The method of  claim 1 , further comprising correlating the presence or absence of the polymorphism with an altered risk for stroke. 
     
     
         13 . The method of  claim 12 , wherein said correlating step is performed by computer software. 
     
     
         14 . The method of  claim 1 , wherein said testing is performed using sequencing, 5′ nuclease digestion, molecular beacon assay, oligonucleotide ligation assay, size analysis, single-stranded conformation polymorphism analysis, or denaturing gradient gel electrophoresis (DGGE). 
     
     
         15 . The method of any one of  claim 1 , wherein said testing is performed using an allele-specific method. 
     
     
         16 . The method of  claim 15 , wherein said allele-specific method is allele-specific probe hybridization, allele-specific primer extension, or allele-specific amplification. 
     
     
         17 . The method of  claim 16 , wherein the method is performed using an allele-specific primer provided in Table 3. 
     
     
         18 . (canceled) 
     
     
         19 . The method of  claim 1 , further comprising correlating the presence of the polymorphism with a reduction of risk for stroke by an HMG-CoA reductase inhibitor. 
     
     
         20 . The method of  claim 19 , wherein said correlating step is performed by computer software. 
     
     
         21 . The method of  claim 19 , wherein said HMG-CoA reductase inhibitor is a hydrophilic statin. 
     
     
         22 . The method of  claim 19 , wherein said HMG-CoA reductase inhibitor is a hydrophobic statin. 
     
     
         23 . The method of  claim 19 , wherein said HMG-CoA reductase inhibitor is selected from the group consisting of pravastatin, atorvastatin, simvastatin, cerevastatin, lovastatin, storvastatin, rosuvastatin, and fluvastatin, or a combination thereof. 
     
     
         24 - 41 . (canceled)