Methods and Compositions for Determining Predisposition to Inflammation-Mediated Cardiovascular Disease

Abstract

The present invention provides methods and compositions for detecting a predisposition to an inflammation-mediated cardiovascular disease in a human subject by detecting a level of leukotriene C4 synthase (LTC4S) gene product in a sample from a human subject indicative of a predisposition to an inflammation-mediated cardiovascular disease or detecting the presence or absence of an allele of LTC4S indicative of a predisposition to an inflammation-mediated cardiovascular disease. In addition, the present invention also provides kits for practicing the methods.

1 . A method of detecting a predisposition to an inflammation-mediated cardiovascular disease in a human subject, said method comprising:
 detecting a level of leukotriene C4 synthase (LTC4S) gene product in a sample from a human subject,   wherein an increased level of LTC4S gene product as compared to a reference level known to be associated with a non-risk of development of an inflammation-mediated cardiovascular disease indicates that the human subject has a predisposition to an inflammation-mediated cardiovascular disease.   
     
     
         2 . The method of  claim 1 , wherein the gene product is nucleic acid. 
     
     
         3 . The method of  claim 2 , wherein the detecting step comprises a polymerase chain reaction or hybridization. 
     
     
         4 . The method of  claim 1 , wherein the gene product is a polypeptide. 
     
     
         5 . The method of  claim 4 , wherein the detecting is by immunoassay. 
     
     
         6 . The method of  claim 1 , wherein the inflammation-mediated cardiovascular disease is atherosclerosis. 
     
     
         7 . The method of  claim 1 , wherein the human subject is a female human subject. 
     
     
         8 . A method of detecting a predisposition to an inflammation-mediated cardiovascular disease in a human subject, said method comprising:
 detecting the presence or absence of an allele of a leukotriene C4 synthase (LTC4S) indicative of a predisposition to an inflammation-mediated cardiovascular disease,   wherein the presence of the allele indicates the human subject has a predisposition to an inflammation-mediated cardiovascular disease.   
     
     
         9 . The method of  claim 8 , wherein the detecting comprises determining the subject's LTC4S promoter region genotype. 
     
     
         10 . The method of  claim 8 , wherein, the allele of LTC4S indicative of a predisposition to an inflammation-mediated cardiovascular disease comprises a cytosine at position −444. 
     
     
         11 . The method of  claim 8 , wherein the detecting comprises a polymerase chain reaction. 
     
     
         12 . The method of  claim 8 , wherein the inflammation-mediated cardiovascular disease is atherosclerosis. 
     
     
         13 . The method of  claim 8 , wherein the human subject is a female human subject. 
     
     
         14 - 18 . (canceled) 
     
     
         19 . A kit for use in detecting a predisposition to an inflammation-mediated cardiovascular disease in a human subject, said kit comprising:
 reagents for assaying a sample for a leukotriene C4 synthase (LTC4S) gene product, and   a reference known to be associated with a non-risk of development of an inflammation-mediated cardiovascular disease.   
     
     
         20 . The kit of  claim 19 , wherein the LTC4S gene product is a nucleic acid. 
     
     
         21 . The kit of  claim 19 , wherein the LTC4S gene product is a polypeptide. 
     
     
         22 . The kit of  claim 19 , wherein the reagents comprise at least one LTC4S gene product affinity reagent. 
     
     
         23 . The kit of  claim 22 , wherein the LTC4S gene product affinity reagent comprises a forward primer and a reverse primer. 
     
     
         24 . The kit of  claim 22 , wherein the LTC4S gene product affinity reagent comprises a nucleic acid complementary to a LTC4S nucleic acid gene product. 
     
     
         25 . The kit of  claim 22 , wherein the LTC4S gene product affinity reagent comprises an anti-LTC4S polypeptide antibody or binding fragment thereof.