Method of predicting a predisposition to qt prolongation

Abstract

The present invention describes an association between genetic polymorphisms in the ceramide kinase-like (CERKL) gene and a predisposition to prolongation of the QT interval, and provides related methods for the prediction of such a predisposition, the administration of QT interval-prolonging compounds to individuals having such a predisposition, and determining whether a compound is capable of inducing QT prolongation.

What is claimed is: 
     
         1 . A method of administering to an individual a compound capable of prolonging the individual's QT interval, the method comprising:
 characterizing an expression product of an individual's ceramide kinase-like (CERKL) gene; and   in the case that the characterized expression product is associated with an increased risk of QT prolongation, administering to the individual a quantity of the compound less than would be administered to an individual having an expression product not associated with an increased risk of QT prolongation.   
     
     
         2 . The method of  claim 1 , wherein the expression product includes at least one expression product selected from the group consisting of: mRNA, a peptide, and a protein. 
     
     
         3 . A method of determining whether a compound is capable of prolonging a QT interval in an individual, the method comprising:
 measuring an expression product of the individual's ceramide kinase-like (CERKL) gene;   administering to the individual a quantity of the compound;   remeasuring the expression product of the individual's CERKL gene; and   determining whether the compound is capable of prolonging the individual's QT interval based on a difference in the measurements of the expression product of the individual's CERKL gene.   
     
     
         4 . The method of  claim 3 , wherein the expression product includes at least one expression product selected from the group consisting of: mRNA, a peptide, and a protein. 
     
     
         5 . A method of determining whether a compound is capable of prolonging a QT interval in an individual, the method comprising:
 measuring a QT interval of each of a plurality of test organisms, the plurality including a first test organism having a ceramide kinase-like (CERKL) genotype associated with a predisposition for prolongation of QT interval and a second organism having a CERKL genotype not associated with a predisposition for prolongation of QT interval;   administering a quantity of the compound to each of the plurality of test organisms;   remeasuring a QT interval of at least the first test organism; and   determining that the compound is capable of prolonging a QT interval in an individual in the case that the remeasured QT interval is greater than the measured QT interval.   
     
     
         6 . The method of  claim 5 , wherein each of the plurality of test organisms is selected from the group consisting of: humans, animals, and cell lines.