Genetic polymorphisms associated with coronary events and drug response, methods of detection and uses thereof

Abstract

The present invention provides compositions and methods based on genetic polymorphisms that are associated with coronary heart disease (particularly myocardial infarction), aneurysm/dissection, and/or response to drug treatment, particularly statin treatment. For example, the present invention relates to nucleic acid molecules containing the polymorphisms, variant proteins encoded by these nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and variant proteins, and methods of using the nucleic acid molecules and proteins as well as methods of using reagents for their detection.

1 - 7 . (canceled) 
     
     
         8 . A method for identifying a human who is in need of receiving treatment for CHD or aneurysm/dissection, comprising detecting a SNP as specified in any one of the nucleic acid sequences of SEQ ID NOS:1 and 3-132, in a sample from said human, and treating said human with a therapeutic agent. 
     
     
         9 . The method of  claim 8  wherein said therapeutic agent is selected from the group consisting of chemical entities and antibodies. 
     
     
         10 . The method of  claim 8 , wherein the therapeutic agent is a statin. 
     
     
         11 - 12 . (canceled) 
     
     
         13 . A method for determining an individual's risk for a cardiovascular event, the method comprising determining which allele is present at at least one SNP selected from the group consisting of rs20455, rs2894424, rs9462535, rs11751357, rs4535541, rs12175497, rs728218, rs2281686, rs35268572, rs9471032, rs9357303, rs9471078, rs9394587, rs4711595, rs11751690, rs9471077, rs9394584, rs11755763, and rs9471080, wherein the presence of the allele is indicative of an altered risk for the cardiovascular event. 
     
     
         14 . The method of  claim 13 , wherein the altered risk is an increased risk. 
     
     
         15 . The method of  claim 13 , wherein the altered risk is a decreased risk. 
     
     
         16 . The method of  claim 13 , wherein the cardiovascular event is a coronary event. 
     
     
         17 . The method of  claim 16 , wherein the coronary event is selected from the group consisting of CHD, aneurysm, and dissection. 
     
     
         18 . The method of  claim 17 , wherein the coronary event is CHD, and further wherein the CHD is MI. 
     
     
         19 - 20 . (canceled) 
     
     
         21 . A method for predicting an individual's response to a drug treatment, the method comprising determining which allele is present at at least one SNP selected from the group consisting of rs20455, rs2894424, rs9462535, rs11751357, rs4535541, rs12175497, rs728218, rs2281686, rs35268572, rs9471032, rs9357303, rs9471078, rs9394587, rs4711595, rs11751690, rs9471077, rs9394584, rs11755763, and rs9471080, wherein the presence of the allele is indicative of an altered response to the drug treatment. 
     
     
         22 . The method of  claim 21 , wherein the drug treatment comprises statin treatment. 
     
     
         23 . The method of  claim 22 , wherein the statin is selected from the group consisting of pravastatin and atorvastatin. 
     
     
         24 . The method of  claim 22 , wherein the statin is selected from the group consisting of fluvastatin, lovastatin, rosuvastatin, and simvastatin. 
     
     
         25 . The method of  claim 22 , wherein the statin treatment comprises a statin in combination with at least one additional therapeutic agent. 
     
     
         26 . The method of  claim 25 , wherein the statin treatment is selected from the group consisting of:
 simvastatin in combination with ezetimibe;   lovastatin in combination with niacin extended-release; and   atorvastatin in combination with amlodipine besylate.   
     
     
         27 - 28 . (canceled) 
     
     
         29 . The method of  claim 22 , wherein the statin treatment is for the prevention or treatment of CHD, aneurysm/dissection, or cancer. 
     
     
         30 . The method of  claim 13 , further comprising providing a report of the individual's risk for the cardiovascular event based on the allele present at the SNP. 
     
     
         31 . The method of  claim 21 , further comprising providing a report of the individual's response to the drug treatment based on the allele present at the SNP. 
     
     
         32 . The method of  claim 31 , further comprising transmitting the report to the individual or to a medical practitioner.