Analysis and use of PAR1 polymorphisms for evaluating the risk of cardiovascular disorders

Abstract

The invention relates to polynucleotide sequences comprising genetic variations of the PAR1 gene at positions 3090 and/or 3329. The occurrence of these variants in humans correlates with increased occurrence of particular cardiovascular disorders. The invention furthermore relates to methods for detecting said genetic variations for the purpose of patient diagnosis.

1 . An isolated polynucleotide sequence which is a polymorphism of a PAR1 gene, wherein the isolated polynucleotide sequence comprises SEQ ID NO: 4.  
     
     
         2 . An isolated polynucleotide sequence which is a polymorphism of the PAR1 gene, wherein the isolated polynucleotide sequence comprises SEQ ID NO: 8.  
     
     
         3 . An isolated polynucleotide sequence which is a polymorphism of the PAR1 gene, wherein the polynucleotide sequence comprises that portion of SEQ ID NO: 4 from nucleotide 3090 to nucleotide 3329.  
     
     
         4 . A method of determining a patient's relative risk of a cardiovascular disorder, comprising 
 a. obtaining a nucleic acid sample from the patient; and    b. determining the presence in the nucleic acid sample of at least one single nucleotide polymorphism of the PAR1 gene sequence, selected from the group of polymorphisms corresponding to a C for T substitution at position 3090 and a C for A substitution at position 3329 of SEQ ID NO: 1;    wherein the presence of the at least one polymorphism is diagnostic of a patient's relative risk of atrial fibrillation, acute coronary syndrome, cardiomyopathy or unstable angina.    
     
     
         5 . The method of  claim 4 , wherein the step of determining the presence of at least one single nucleotide polymorphism comprises amplification of a portion of the nucleic acid sample comprising position 3090 of SEQ ID NO: 1 by polymerase chain reaction.  
     
     
         6 . The method of  claim 4 , wherein the step of determining the presence of at least one single nucleotide polymorphism comprises amplification of a portion of the nucleic acid sample comprising position 3329 of SEQ ID NO: 1 by polymerase chain reaction.  
     
     
         7 . The method of  claim 4 , wherein the step of determining the presence of at least one single nucleotide polymorphism comprises sequencing of a portion of the nucleic acid sample comprising position 3090 of SEQ ID NO: 1.  
     
     
         8 . The method of  claim 4 , wherein the step of determining the presence of at least one single nucleotide polymorphism comprises sequencing of a portion of the nucleic acid sample comprising position 3329 of SEQ ID NO: 1.