Compositions and methods for diagnosing and treating arrhythmias

Abstract

The present invention relates to compositions and methods for diagnosing and treating arrhythmias. In particular, the present invention provides IL-18 markers and uses thereof.

What is claimed is: 
     
         1 . A method of preventing or treating ventricular arrhythmia, comprising: administering an anti-IL-18 agent to a subject diagnosed or at risk for ventricular arrhythmia. 
     
     
         2 . The method of  claim 1 , wherein said anti-IL-18 treatment is selected from the group consisting of a nucleic acid, an antibody, and a small molecule. 
     
     
         3 . The method of  claim 2 , wherein said antibody is interleukin 18 binding protein (IL18BP) or IL-18ab. 
     
     
         4 . The method of  claim 2 , wherein said small molecule is hydroxyurea or decitabine. 
     
     
         5 . The method of  claim 1 , wherein said subject has sickle cell disease, sickle cell trait, hemolytic anemia, or increased levels of heme or IL-18 in circulation, blood samples, or tissue 
     
     
         6 . The method of  claim 1 , wherein said subject comprises a variant IL-18 gene. 
     
     
         7 . The method of  claim 6 , wherein said variant IL-18 gene comprises a genotype of C/T at rs5744285. 
     
     
         8 . The method of  claim 6 , wherein said IL-18 gene further comprises one or more additional variants, wherein said variants comprise a genotype selected from the group consisting of T/C or C/C at rs11214107; a haplotype of C/T at rs5744285 and T/C or C/C at rs11214107; a haplotype of T/C or C/C at rs11214107 and A/G or A/A at rs12796114; and a haplotype of T/C at rs5744285 and T/C or C/C at rs80008802. 
     
     
         9 . The method of  claim 6 , wherein said variant IL-18 gene is detected using a nucleic acid reagent is selected from the group consisting of a) at least one nucleic acid probe that hybridizes to a C allele at rs5744285 and at least one nucleic acid probe that hybridizes to a T allele at rs5744285; b) at least one pair of nucleic acid primers that hybridize to a C allele at rs5744285 and at least one pair of nucleic acid primers that hybridize to a T allele at rs5744285; and c) at least one nucleic acid primer that hybridizes to a C allele at rs5744285 and at least one nucleic acid primer that hybridizes to a T allele at rs5744285 
     
     
         10 . The method of  claim 9 , wherein said nucleic acid reagent is detectably labelled. 
     
     
         11 . The method of  claim 6 , wherein said variant IL-18 gene is detected using a detection technique selected from the group consisting of a hybridization assay, a sequencing assay, and an amplification assay.