Methods and compositions for scd, crt, crt-d, or sca therapy identification and/or selection

Abstract

Compositions, polynucleotides, probes, kits, methods, computer systems, treatment methods and genetic markers useful for assessing the risk of Sudden Cardiac Death (SCD), Sudden Cardiac Arrest (SCA), Ventricular Arrhythmia (VA), or Heart Failure (HF) are provided herein. The compositions, polynucleotides, probes, kits, methods, computer systems, treatment methods and genetic markers of the invention can provide patients selection for those that can be treated with an ICD or CRT-D based on assessing the presence of one or more Single Nucleotide Polymorphisms (SNPs) associated with any one of Sudden Cardiac Death (SCD), Sudden Cardiac Arrest (SCA), Ventricular Arrhythmia (VA), or Heart Failure (HF), and can indicate treatment with certain drugs such as beta-blockers.

We claim: 
     
         1 . A diagnostic kit, comprising:
 at least one probe for assessing the presence of one or more Single Nucleotide Polymorphisms (SNPs) associated with any one of Sudden Cardiac Arrest (SCA), Sudden Cardiac Death (SCD), Ventricular Arrhythmia (VA), or Heart Failure (HF) in a genetic sample,   wherein the SNP is contained in any one of the nucleotide sequences of SEQ ID NO.'s 1-2; and   wherein Sudden Cardiac Arrest (SCA), Sudden Cardiac Death (SCD), Ventricular Arrhythmia (VA) or Heart Failure (HF) is treatable with a combination CRT pacemaker having defibrillation technology (CRT-D), an Implantable Cardioverter Defibrillator (ICD), pharmacological therapy, or biological therapy.   
     
     
         2 . The diagnostic kit of  claim 1 , wherein at least one probe overlaps a polymorphic position in any one of SEQ ID NO.'s 1-2 where the polymorphic position is flanked on either the 5′ and 3′ side by a single base pair, to any number of base pairs flanking the 5′ and 3′ side of the polymorphic position sufficient to identify the SNP or result in a hybridization. 
     
     
         3 . The diagnostic kit of  claim 2 , wherein the polymorphic position is at position 26 or 27. 
     
     
         4 . The diagnostic kit of  claim 2 , said at least one probe having a length selected from the group of 12 to 101, 25 to 35, 18 to 30, 17 to 24, 15 to 101, 17 to 101, 19 to 101, 21 to 101, 24 to 101, 26 to 101, 15 to 50, 17 to 50, 19 to 50, 21 to 50, 24 to 50, and 26 to 50 nucleotides. 
     
     
         5 . The diagnostic kit of  claim 1 , further comprising a Polymerase Chain Reaction (PCR) primer set for amplifying nucleic acid fragments corresponding to any one of SEQ ID NO.'s 1-2. 
     
     
         6 . The diagnostic kit of  claim 1 , wherein said at least one probe has a label capable of being detected by electrical, fluorescent or radioactive means. 
     
     
         7 . The diagnostic kit of  claim 1 , wherein said at least one probe is affixed to a substrate. 
     
     
         8 . The diagnostic kit of  claim 1 , further comprising a computer processor programmed with software for extracting information of a hybridization of said at least one probe in the diagnostic kit. 
     
     
         9 . The diagnostic kit of  claim 1 , wherein said at least one probe is an Allele Specific Oligomer (ASO). 
     
     
         10 . The diagnostic kit of  claim 1 , wherein the SNP is bi-allelic. 
     
     
         11 . The diagnostic kit of  claim 1 , wherein the SNP is multi-allelic. 
     
     
         12 . The diagnostic kit of  claim 1 , wherein said at least one probe is selected from the group of sense, anti-sense, and naturally occurring mutants, of any one of SEQ ID NO.'s 1-2. 
     
     
         13 . A system for detecting one or more Single Nucleotide Polymorphisms (SNPs) associated with Sudden Cardiac Arrest (SCA), Sudden Cardiac Death (SCD), Ventricular Arrhythmia (VA) or Heart Failure (HF), comprising a computer system, having a computer processor programmed with an algorithm, and one or more genetic databases that are in communication with the programmed processor, wherein the programmed computer processor is used to impute p-values for one or more known SNPs detected in DNA contained in one or more genetic samples obtained from a patient and/or from the one or more genetic databases. 
     
     
         14 . A method, comprising:
 detecting one or more Single Nucleotide Polymorphisms (SNPs) associated with Sudden Cardiac Arrest (SCA), Sudden Cardiac Death (SCD), Ventricular Arrhythmia (VA) or Heart Failure (HF) by utilizing at least one probe that overlaps a polymorphic position in any one of SEQ ID NO.'s 1-2 where the polymorphic position is flanked on either the 5′ and 3′ side by a single base pair, to any number of base pairs flanking the 5′ and 3′ side of the polymorphic position sufficient to identify the SNP or result in a hybridization; and   assessing the presence of hybridization of the at least one probe.   
     
     
         15 . The method of  claim 14 , wherein the one or more SNPs comprise at least one of a TT genotype of subunit C393T of the GNAS gene and a TT genotype of subunit C2273T of the GNAS gene. 
     
     
         16 . The method of  claim 14 , wherein the at least one probe has a length selected from the group of 12 to 101, 25 to 35, 18 to 30, 17 to 24, 15 to 101, 17 to 101, 19 to 101, 21 to 101, 24 to 101, 26 to 101, 15 to 50, 17 to 50, 19 to 50, 21 to 50, 24 to 50, and 26 to 50 nucleotides. 
     
     
         17 . The method of  claim 14 , wherein the at least one probe is capable of being detected by electrical, fluorescent or radioactive means. 
     
     
         18 . The method of  claim 14 , further comprising the step of amplifying a DNA sample prior to utilizing the at least one probe. 
     
     
         19 . The method of  claim 18 , wherein the amplified DNA sample is labeled with a detectable label, and the at least one probe is immobilized to a known location on a solid support; and
 wherein assessing the presence of hybridization of the at least one probe comprises detecting the location of the detectable label with respect to the solid support;   wherein the detectable label is detectable by at least one of by spectroscopic, photochemical, biochemical, immunochemical, electrical, optical, and chemical means.   
     
     
         20 . The method of  claim 14 , wherein the polymorphic position is at position 26 or 27.