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

Abstract

This 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.

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 - 8 . (canceled) 
     
     
         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 - 16 . (canceled) 
     
     
         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 - 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 . A method of treatment comprising:
 selecting a human subject on the basis that the human subject has an Apo(a) polymorphism characterized by thymine or adenine at chromosome 6:160880877 (March 2006 assembly—NCBI build 36.1; rs3798220 dbSNP @ NCBI), and   administering to the subject an anti-platelet agent or an antithrombotic agent other than acetylsalicylic acid for reducing the risk of a future cardiovascular event because the subject has the polymorphism.   
     
     
         25 . The method of  claim 24 , wherein the antithrombotic agent is a thienopyridine or a thienopyridine derivative. 
     
     
         26 . The method of  claim 25 , wherein the thienopyridine or thienopyridine derivative is clopidogrel, clopidogrel bisulfate, ticlopidine, prasugrel (CS-747, or LY 640315), SR 25989, or PCR 4099. 
     
     
         27 . The method of  claim 24 , wherein the antithrombotic agent is cenoxaparin sodium, ximelagatran, abciximab or tirofiban. 
     
     
         28 . A method for evaluating a human subject's responsiveness to acetylsalicylic acid treatment to reduce the risk of a future cardiovascular event comprising:
 detecting the presence or absence of a genetic marker linked or in linkage disequilibrium with a single nucleotide polymorphism (SNP) 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.   
     
     
         29 . (canceled) 
     
     
         30 . The method of  claim 28 , wherein the genetic marker is a SNP at position chromosome 6:160849894 (NCBI build 128; rs9457931 dbSNP@NCBI). 
     
     
         31 . The method of  claim 28 , wherein the genetic marker is a SNP at position chromosome 6:160830272 (NCBI build 128; rs9457927 dbSNP@NCBI). 
     
     
         32 . (canceled) 
     
     
         33 . The method of  claim 28 , wherein the presence of a polymorphism characterized by cytosine or guanine at the position chromosome 6:160880877 indicates responsiveness to acetylsalicylic acid. 
     
     
         34 . The method of  claim 28 , wherein the presence of a polymorphism characterized by thymine or adenine at the position chromosome 6:160880877 indicates non-responsiveness to acetylsalicylic acid. 
     
     
         35 - 41 . (canceled) 
     
     
         42 . A method for evaluating a human subject's 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) gene, and   determining a level of Lipoprotein(a) (Lp(a)) in a blood sample from the human subject.   
     
     
         43 . The method of  claim 42 , wherein the presence of a polymorphism characterized by cytosine or guanine at the position chromosome 6:160880877 and the presence of an elevated level of Lp(a) in the blood sample from the subject indicates that the subject is at an elevated risk of a future cardiovascular event. 
     
     
         44 - 47 . (canceled) 
     
     
         48 . The method of  claim 42 , wherein the cardiovascular event is myocardial infarction, stroke, cardiovascular death, coronary re-stenosis, coronary stent re-stenosis, coronary stent re-thrombosis, revascularization, pulmonary embolism, or venous thrombosis.