GENETIC MARKERS FOR RISK MANAGEMENT OF CARDIAC ARRHYTHMIA
First Claim
1. A method of determining a susceptibility to cardiac arrhythmia or stroke in a human individual, the method comprising determining the presence or absence of at least one allele of at least one polymorphic marker in a nucleic acid sample from the individual, wherein the at least one polymorphic marker is selected from the polymorphic markers set forth in Table 5, and markers in linkage disequilibrium therewith,and wherein determination of the presence or absence of the at least one allele is indicative of a susceptibility to cardiac arrhythmia or stroke in the individual.
2 Assignments
0 Petitions
Accused Products
Abstract
The invention relates to procedure and methods of determining a susceptibility to cardiac arrhythmia, including Atrial Fibrillation, Atrial Flutter and Stroke, by assessing the presence or absence of alleles at polymorphic markers found to be associated with Atrial Fibrillation, Atrial Flutter and Stroke. The invention further relates to kits encompassing reagents for assessing such markers, and diagnostic methods, uses and procedures for utilizing such susceptibility markers.
-
Citations
77 Claims
-
1. A method of determining a susceptibility to cardiac arrhythmia or stroke in a human individual, the method comprising determining the presence or absence of at least one allele of at least one polymorphic marker in a nucleic acid sample from the individual, wherein the at least one polymorphic marker is selected from the polymorphic markers set forth in Table 5, and markers in linkage disequilibrium therewith,
and wherein determination of the presence or absence of the at least one allele is indicative of a susceptibility to cardiac arrhythmia or stroke in the individual.
-
2. A method of determining a susceptibility to cardiac arrhythmia or stroke in a human individual, comprising determining whether at least one at-risk allele in at least one polymorphic marker is present in a genotype dataset derived from the individual, wherein the at least one polymorphic marker is selected from the markers set forth in Table 5, and markers in linkage disequilibrium therewith, and wherein determination of the presence of the at least one at-risk allele is indicative of increased susceptibility to cardiac arrhythmia or stroke in the individual.
-
11. A method of assessing a susceptibility to cardiac arrhythmia or stroke in a human individual, comprising screening a nucleic acid from the individual for at least one polymorphic marker allele or haplotype in SEQ ID NO:
- 50 that correlates with increased occurrence of cardiac arrhythmia or stroke in a human population;
wherein determination of the presence of an at-risk marker allele in the at least one polymorphism or an at-risk haplotype in the nucleic acid identifies the individual as having elevated susceptibility to cardiac arrhythmia and/or stroke, and wherein the absence of the at least one at-risk marker allele or at-risk haplotype in the nucleic acid identifies the individual as not having the elevated susceptibility.
- 50 that correlates with increased occurrence of cardiac arrhythmia or stroke in a human population;
-
12-15. -15. (canceled)
-
16. A method of identification of a marker for use in assessing susceptibility to cardiac arrhythmia and/or stroke in human individuals, the method comprising
a. identifying at least one polymorphic marker within SEQ ID NO: - 50, or at least one polymorphic marker in linkage disequilibrium with at least one marker within SEQ ID NO;
50;b. determining the genotype status of a sample of individuals diagnosed with cardiac arrhythmia and/or stroke; and c. determining the genotype status of a sample of control individuals; wherein a significant difference in frequency of at least one allele in at least one polymorphism in individuals diagnosed with cardiac arrhythmia and/or stroke as compared with the frequency of the at least one allele in the control sample is indicative of the at least one polymorphism being useful for assessing susceptibility to cardiac arrhythmia and/or stroke. - View Dependent Claims (17)
- 50, or at least one polymorphic marker in linkage disequilibrium with at least one marker within SEQ ID NO;
-
18-19. -19. (canceled)
-
20. A method of genotyping a nucleic acid sample obtained from a human individual, comprising determining the presence or absence of at least one allele of at least one polymorphic marker predictive of increased risk of cardiac arrhythmia and/or stroke in the sample, wherein the at least one marker is selected from the markers set forth in Table 5, and markers in linkage disequilibrium therewith, and wherein determination of the presence or absence of the at least one allele of the at least one polymorphic marker is predictive of increased risk of cardiac arrhythmia and/or stroke in the individual.
-
21-25. -25. (canceled)
-
26. A method of determining a susceptibility to cardiac arrhythmia or stroke in a human individual, the method comprising determining the identity of at least one allele of at least one polymorphic marker in a nucleic acid sample obtained from the individual, wherein the at least one marker is selected from the group of markers associated with the PITX2 gene, wherein the presence of the at least one allele is indicative of a susceptibility to cardiac arrhythmia or stroke in the individual.
-
27-29. -29. (canceled)
-
36. A method of assessing an individual for probability of response to a therapeutic agent for preventing and/or ameliorating symptoms associated with cardiac arrhythmia and/or stroke, comprising:
- determining the presence or absence of at least one allele of at least one polymorphic marker in a nucleic acid sample obtained from the individual, wherein the at least one polymorphic marker is selected from the markers set forth in Table 9, and markers in linkage disequilibrium therewith, wherein determination of the presence of the at least one allele of the at least one marker is indicative of a probability of a positive response to the therapeutic agent for cardiac arrhythmia and/or stroke.
- View Dependent Claims (37, 38, 39)
-
40. A method of predicting prognosis of an individual diagnosed with, cardiac arrhythmia and/or stroke, the method comprising determining the presence or absence of at least one allele of at least one polymorphic marker in a nucleic acid sample obtained from the individual, wherein the at least one polymorphic marker is selected from the markers set forth in Table 9, and markers in linkage disequilibrium therewith, wherein determination of the presence of the at least one allele is indicative of a worse prognosis of the cardiac arrhythmia and/or stroke in the individual.
-
41. A method of monitoring progress of a treatment of an individual undergoing treatment for cardiac arrhythmia and/or stroke, the method comprising determining the presence or absence of at least one allele of at least one polymorphic marker in a nucleic acid sample obtained from the individual, wherein the at least one polymorphic marker is selected from the markers set forth in Table 9, and markers in linkage disequilibrium therewith, wherein determination of the presence of the at least one allele is indicative of the treatment outcome of the individual.
-
42-48. -48. (canceled)
-
51-52. -52. (canceled)
-
53. A kit for assessing susceptibility to cardiac arrhythmia and/or stroke in a human individual, the kit comprising reagents for selectively detecting at least one allele of at least one polymorphic marker in the genome of the individual, wherein the polymorphic marker is selected from the group consisting of the polymorphic markers within the segment whose sequence is set forth in SEQ ID NO:
- 50, and markers in linkage disequilibrium therewith, and wherein the presence of the at least one allele is indicative of a susceptibility to cardiac arrhythmia and/or stroke.
- View Dependent Claims (60, 63, 64)
-
54-59. -59. (canceled)
-
61-62. -62. (canceled)
-
65. (canceled)
-
66. Use of an oligonucleotide probe in the manufacture of a diagnostic reagent for diagnosing and/or assessing susceptibility to cardiac arrhythmia and/or stroke in a human individual, wherein the probe hybridizes to a segment of a nucleic acid whose nucleotide sequence is given by SEQ ID NO:
- 50 that comprises at least one polymorphic site, wherein the fragment is 15-500 nucleotides in length.
-
67-71. -71. (canceled)
-
72. A computer-readable medium on which is stored:
-
a. an identifier for at least one polymorphic marker; b. an indicator of the frequency of at least one allele of said at least one polymorphic marker in a plurality of individuals diagnosed with atrial fibrillation, atrial flutter and/or stroke; and c. an indicator of the frequency of the least one allele of said at least one polymorphic markers in a plurality of reference individuals; wherein the at least one polymorphic marker is selected from the polymorphic markers set forth in Table 5, and polymorphisms in linkage disequilibrium therewith.
-
-
73-74. -74. (canceled)
-
75. An apparatus for determining a genetic indicator for cardiac arrhythmia and/or stroke in a human individual, comprising:
-
a computer readable memory; and a routine stored on the computer readable memory; wherein the routine is adapted to be executed on a processor to analyze genotype and/or haplotype data for at least one human individual with respect to at least one polymorphic marker selected from the markers set forth in Table 5, and markers in linkage disequilibrium therewith, and generate an output based on the marker or haplotype data, wherein the output comprises a risk measure of the at least one marker or haplotype as a genetic indicator of cardiac arrhythmia and/or stroke for the human individual. - View Dependent Claims (76)
-
-
77-79. -79. (canceled)
Specification