Polymorphism in the apo(a) gene predict responsiveness to acetylsalicylic acid treatment

Abstract

The invention relates to nucleotide polymorphisms in the human Apo(a) gene and to the use of Apo(a) nucleotide polymorphisms in identifying whether a human subject will respond or not to treatment with acetylsalicylic acid.

We claim: 
     
         1 . A method for evaluating a human subject's responsiveness to acetylsalicylic acid treatment to reduce the risk of a future cardiovascular event comprising:
 determining the identity of a single nucleotide polymorphism at position chromosome 6:160880877 (March 2006 assembly—NCBI build 36.1; rs3798220 dbSNP @ NCBI) of the human subject's apolipoprotein(a) (Apo(a)) gene.   
     
     
         2 . The method of  claim 1 , wherein the presence of a polymorphism characterized by cytosine or guanine at the position chromosome 6:160880877 indicates responsiveness to acetylsalicylic acid. 
     
     
         3 . The method of  claim 1 , further comprising determining a level of Lipoprotein(a) (Lp(a)) in a blood sample from the subject. 
     
     
         4 . The method of  claim 3 , wherein the subject has an elevated level of Lp(a) in the blood. 
     
     
         5 . The method of  claim 4 , wherein the level of Lp(a) is about 10 mg/dl or higher in the blood sample from the subject. 
     
     
         6 . The method of  claim 4 , wherein the level of Lp(a) is about 15 mg/dl or higher in the blood sample from the subject. 
     
     
         7 . The method of  claim 4 , wherein the level of Lp(a) is about 20 mg/dl or higher in the blood sample from the subject. 
     
     
         8 . The method of  claim 4 , wherein the level of Lp(a) is about 25 mg/dl or higher in the blood sample from the subject. 
     
     
         9 . The method of  claim 1 , wherein the presence of a polymorphism characterized by thymine or adenine at the position chromosome 6:160880877 indicates non-responsiveness to acetylsalicylic acid. 
     
     
         10 . The method of  claim 1 , wherein the cardiovascular event is myocardial infarction, stroke, acute coronary syndrome, myocardial ischemia, chronic stable angina pectoris, unstable angina pectoris, cardiovascular death, coronary re-stenosis, coronary stent re-stenosis, coronary stent re-thrombosis, revascularization, angioplasty, transient ischemic attack, pulmonary embolism, vascular occlusion, or venous thrombosis. 
     
     
         11 . The method of  claim 1 , wherein the identity of the polymorphism is determined by contacting a nucleic acid obtained from the subject with a nucleic acid probe. 
     
     
         12 . The method of  claim 1 , wherein the identity of the polymorphism is determined by allele-specific probe hybridization, allele-specific primer extension, allele-specific amplification, 5′ nuclease digestion, molecular beacon assay, oligonucleotide ligation assay, size analysis, or single-stranded conformation polymorphism. 
     
     
         13 . The method of  claim 1 , wherein the identity of the polymorphism is determined by sequencing a nucleic acid obtained from the subject. 
     
     
         14 . An assay comprising:
 contacting an agent with an apolipoprotein(a) (Apo(a)) protein encoded by an (Apo(a)) gene having nucleotide cytosine or guanine at chromosome 6:160880877 (March 2006 assembly—NCBI build 36.1; rs3798220 dbSNP @ NCBI),   evaluating binding of the agent to the isolated Apo(a) protein or to Lipoprotein(a) (Lp(a)), and   comparing the binding to a control.   
     
     
         15 . (canceled) 
     
     
         16 . The assay of any one of  claim 14 , wherein the control comprises a measurement of binding of acetylsalicylic acid to the isolated Apo(a) protein to Lp(a) or to platelets, or a measurement of acetylsalicylic acid interaction with platelets. 
     
     
         17 . A method of treatment comprising:
 selecting a human subject on the basis that the human subject has an Apo(a) polymorphism characterized by cytosine or guanine at chromosome 6:160880877 (March 2006 assembly—NCBI build 36.1; rs3798220 dbSNP @ NCBI), and   administering to the subject acetylsalicylic acid for reducing the risk of a future cardiovascular event because the subject has the polymorphism.   
     
     
         18 . The method of  claim 17 , wherein the human subject also has an elevated level of Lipoprotein(a) (Lp(a)) in the blood. 
     
     
         19 . The method of  claim 18 , wherein the level of Lp(a) is about 10 mg/dl or higher in a blood sample from the subject. 
     
     
         20 . The method of  claim 19 , wherein the level of Lp(a) is about 15 mg/dl or higher in a blood sample from the subject. 
     
     
         21 - 22 . (canceled) 
     
     
         23 . The method of  claim 17 , wherein the cardiovascular event is myocardial infarction, stroke, acute coronary syndrome, myocardial ischemia, chronic stable angina pectoris, unstable angina pectoris, cardiovascular death, coronary re-stenosis, coronary stent re-stenosis, coronary stent re-thrombosis, revascularization, angioplasty, transient ischemic attack, pulmonary embolism, vascular occlusion, or venous thrombosis. 
     
     
         24 - 48 . (canceled)