Method of diagnosis of a predisposition to develop thrombotic disease and its uses

Abstract

The present invention refers to a method of diagnosis of a predisposition to develop thrombotic disease, to test systems and their use for the diagnosis of a predisposition to develop thrombotic disease, to a P2X1 promoter variant and its use for screening for an anti-thrombotic agent, and to methods for identifying an individual that can be prophylactically or therapeutically treated with an anti-thrombotic agent, or for adapting a therapeutic or prophylactic dose of an anti-thrombotic agent.

1 . A test system comprising at least one nucleic acid probe or oligonucleotide used for determining the sequence of at least one allele of the P 2 X 1  promoter at position 304, position 764, position 838, or position 1002 of SEQ ID NO:1 in a tissue sample obtained from an individual. 
     
     
         2 . The test system according to  claim 1  comprising at least one oligonucleotide comprising SEQ ID NO:3 or SEQ ID NO:4 for determining the sequence of the P 2 X 1  promoter of at least one allele at position 304 of SEQ ID NO:1, at least one oligonucleotide comprising SEQ ID NO:5 or SEQ ID NO:6 for determining the sequence of the P 2 X 1  promoter of at least one allele at position 764 of SEQ ID NO:1, at least one oligonucleotide comprising SEQ ID NO:7 or SEQ ID NO:8 for determining the sequence of the P 2 X 1  promoter of at least one allele at position 838 of SEQ ID NO:1, or at least one oligonucleotide comprising SEQ ID NO:9 or SEQ ID NO:10 for determining the sequence of the P 2 X 1  promoter of at least one allele at position 1002 of SEQ ID NO:1. 
     
     
         3 . A method for diagnosis of a predisposition to develop peripheral vascular disease (PVD), stroke, prolonged reversible ischemic neurological deficit (PRIND), transitory ischemic attack (TIA) or myocardial infarction comprising:
 (a) selecting at least one nucleic acid probe or oligonucleotide from the test system of  claim 1 ,   (b) obtaining a tissue sample from an individual, and   (c) determining the sequence of at least one allele of the P 2 X 1  promoter at position 304, position 764, position 838 or position 1002 of SEQ ID NO:1,   wherein (i) a Tat position 304, a C at position 764 or a C at position 1002 indicates a predisposition to PVD, (ii) a C at position 304 or a G at position 764 indicates a predisposition to stroke, PCD or TIA, or (iii) a T at position 838 indicates a predisposition to myocardial infarction.   
     
     
         4 . The test system of  claim 1  further comprising at least one anti-P 2 X 1  antiserum, anti-P 2 X 1  antibody, or anti-P 2 X 1  antibody-fragment for determining the amount of the P 2 X 1  protein in a tissue sample obtained from an individual. 
     
     
         5 . An isolated P 2 X 1  promoter variant comprising at least one T at position 304, C at position 764, T at position 838 or C at position 1002 of SEQ ID NO:1. 
     
     
         6 . The isolated P 2 X 1  promoter variant of  claim 5 , wherein the promoter variant produces a detectable product. 
     
     
         7 . A method of screening for an anti-thrombotic agent, comprising:
 (a) providing the P 2 X 1  promoter variant according to  claim 6 ,   (b) bringing the P 2 X 1  promoter variant into contact with a test compound, and   (c) determining the activity of the P 2 X 1  promoter variant by measuring the detectable product.   
     
     
         8 . A method of screening for an anti-thrombotic agent, wherein the method comprises the steps of:
 (a) providing a P 2 X 1  promoter variant according to  claim 5 ,   (b) bringing the P 2 X 1  promoter variant into contact with a test compound, and   (c) determining the activity of the P 2 X 1  promoter variant.   
     
     
         9 . The method according to  claim 7  or  8  which is adapted to a high-throughput screening of test compounds.