Diagnostic marker and platform for drug design in myocardial infarction and heart failure
AssigneeCentre de Recherche Public de la Sante
InventorDaniel R. WAGNER
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Abstract
Methods for determining the susceptibility of an individual to a heart condition, post myocardial infarction, comprising detecting the presence of an amino acid change in the sequence of the hemopexin domain of MMP-9 (Matrix Metalloproteinase 9), the presence of an amino acid change in said domain being indicative of susceptibility to said heart condition, post myocardial infarction is described, together with methods for drug design.
Claims25
A method for determining the susceptibility of an individual to a heart condition, post myocardial infarction, comprising detecting the presence of an amino acid change in the sequence of the hemopexin domain of MMP-9 (Matrix Metalloproteinase 9), the presence of an amino acid change in said domain being indicative of susceptibility to said heart condition, post myocardial infarction.
A method for assaying for the presence of a first polynucleotide having a SNP associated with susceptibility to a heart condition in a sample, comprising;
- contacting said sample with a second polynucleotide, wherein said second polynucleotide comprises a nucleotide sequence selected from the group consisting SEQ. ID. NOS.:
- 1,3, 5, 7, 9 and/or 10 and the complements of said sequences, wherein said second polynucleotide hybridizes to said first polynucleotide under stringent conditions.
A method of assaying for the presence of a polypeptide encoded by an isolated polynucleotide having a SNP in the hemopexin domain of MMP-9 associated with susceptibility to a heart condition in a sample, said method comprising contacting the sample with an antibody which specifically binds to said encoded polypeptide.
A method of identifying an agent that alters expression of a polynucleotide containing a SNP associated with susceptibility to a heart condition comprising:
- (a) contacting a polynucleotide with an agent to be tested under conditions for expression, wherein the polynucleotide comprises (1) a SNP in the hemopexin domain of MMP-9 associated with susceptibility to a heart condition and (2) a promoter region operably linked to a reporter gene;
- (b) assessing the level of expression of the reporter gene in the presence of the agent;
- (c) assessing the level of expression of the reporter gene in the absence of the agent;
- and
- (d) comparing the level of expression in step (b) with the level of expression in step (c) for differences which indicate that expression was altered by the agent.
A method of diagnosing susceptibility to a heart condition in an individual, comprising:
- a) obtaining a polynucleotide sample from said individual;
- and
- b) analyzing the polynucleotide sample for the presence or absence of a haplotype, wherein the presence of the haplotype corresponds to a susceptibility to said heart condition;
- wherein the haplotype comprises an allele resulting from a SNP in the hemopexin domain of MMP-9 associated with susceptibility to a heart condition.
A vector comprising an isolated polynucleotide containing a SNP in the hemopexin domain of MMP-9 associated with susceptibility to a heart condition, wherein said isolated polynucleotide is operably linked to a regulatory sequence, preferably a suitable promoter.
A transgenic animal comprising a polynucleotide having a SNP in the hemopexin domain of MMP-9 associated with susceptibility to a heart condition.
A kit for assaying a sample for the presence of a first polynucleotide comprising a SNP in the hemopexin domain of MMP-9 associated with susceptibility to a heart condition, comprising in separate containers:
- a) one or more labelled second polynucleotides comprising a sequence selected from the group consisting of sequences identified by SEQ. ID. NOS.:
- 1,3, 5, 7, 9 and/or 10, and the complements thereof;
- and
- b) reagents for detection of said label.
Dependencies are inferred from the claim text.