GENE ASSOCIATED WITH ARTERIOSCLEROTIC DISEASE, AND USE THEREOF
First Claim
1. A method for testing whether or not a subject has a risk factor for arteriosclerotic disease, which uses the subject'"'"'s AGTRL1 gene expression as an index.
5 Assignments
0 Petitions
Accused Products
Abstract
Two genes implicated in arteriosclerotic diseases such as cerebral infarction were successfully identified by performing genome-wide correlation studies using SNPs by targeting the entire genome. Polymorphic mutations that can be used to examine the presence or absence of risk factors for arteriosclerotic diseases were successfully found on the genes. Subjects can be efficiently examined for the presence or absence of risk factors for arteriosclerotic diseases using the presence or absence of the polymorphic mutations as indicators. Furthermore, methods of screening for therapeutic agents for arteriosclerotic diseases are enabled by using expression or function of the genes as index.
5 Citations
39 Claims
- 1. A method for testing whether or not a subject has a risk factor for arteriosclerotic disease, which uses the subject'"'"'s AGTRL1 gene expression as an index.
- 2. A method for testing whether or not a subject has a risk factor for arteriosclerotic disease, which comprises detecting DNA mutation in the subject'"'"'s AGTRL1 gene.
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4. A method for testing whether or not a subject has a risk factor for arteriosclerotic disease, which uses the subject'"'"'s PRKCH gene expression as an index.
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5. A method for testing whether or not a subject has a risk factor for arteriosclerotic disease, which comprises detecting DNA mutation in the subject'"'"'s PRKCH gene.
- 7. A method for testing whether or not a subject has a risk factor for arteriosclerotic disease, wherein the method comprises determining type of nucleotide at a polymorphic site in the subject'"'"'s AGTRL1 gene.
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10. A method for testing whether or not a subject has a risk factor for arteriosclerotic disease, wherein the subject is determined to have a risk factor for arteriosclerotic disease when a DNA block showing the following haplotype is detected:
(A) a haplotype in which the nucleotides in the complementary strand of the AGTRL1 gene at polymorphic sites located at positions 39268, 39353, 41786, 42019, and 43406 of the nucleotide sequence of SEQ ID NO;
1 are A, G, A, G, and C, respectively.
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11. A method for testing whether or not a subject has a risk factor for arteriosclerotic disease, which comprises the step of determining the type of nucleotide of a linked polymorphic site present within a DNA block showing the following haplotype:
(A) a haplotype in which the nucleotides of the complementary strand at polymorphic sites on the AGTRL1 gene located at positions 39268, 39353, 41786, 42019, and 43406 of the nucleotide sequence of SEQ ID NO;
1 are A, G, A, G, and C, respectively.
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12. A method for testing whether or not a subject has a risk factor for arteriosclerotic disease, which comprises the steps of:
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(a) determining the type of nucleotide at a polymorphic site in the AGTRL1 gene of the subject; and (b) determining that the subject has a risk factor for arteriosclerotic disease when the nucleotide determined in (a) is the same as the nucleotide at said polymorphic site in the AGTRL1 gene showing the haplotype of (A); (A) a haplotype in which the nucleotides of the complementary strand at polymorphic sites in the AGTRL1 gene located at positions 39268, 39353, 41786, 42019, and 43406 of the nucleotide sequence of SEQ ID NO;
1 are A, G, A, G, and C, respectively. - View Dependent Claims (13)
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14. A method for testing whether or not a subject has a risk factor for arteriosclerotic disease, wherein the subject is determined to have a risk factor for arteriosclerotic disease when the expression level of the subject'"'"'s AGTRL1 gene is elevated compared to that of a control.
- 15. A method for testing whether or not a subject has a risk factor for arteriosclerotic disease, wherein the method comprises determining the type of nucleotide at a polymorphic site in the subject'"'"'s PRKCH gene.
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18. A method for testing whether or not a subject has a risk factor for arteriosclerotic disease, wherein the subject is determined to have a risk factor for arteriosclerotic disease when the autophosphorylation activity or kinase activity of the subject'"'"'s PRKCH protein is elevated compared to that of a control.
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19. A method for testing whether or not a subject has a risk factor for arteriosclerotic disease, wherein the subject is determined to have a risk factor for arteriosclerotic disease when the subject carries a mutant protein in which valine at position 374 in the amino acid sequence of the PRKCH protein is substituted with isoleucine.
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24. A reagent for testing for the presence or absence of a risk factor for arteriosclerotic disease, which comprises (a) or (b) as an active ingredient:
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(a) an oligonucleotide that hybridizes with a transcript of an AGTRL1 or PRKCH gene; and (b) an antibody that recognizes an AGTRL1 or PRKCH protein.
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25. A reagent for screening for a pharmaceutical agent for treating or preventing arteriosclerotic disease, which comprises any one of (a) to (c) as an active ingredient:
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(a) an oligonucleotide that hybridizes with a transcript of an AGTRL1 gene; (b) an antibody that recognizes an AGTRL1 protein; and (c) a polynucleotide comprising a DNA region which comprises a nucleotide site in a AGTRL1 gene located at position 39353 or 42509 of the nucleotide sequence of SEQ ID NO;
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26. A reagent for screening for a pharmaceutical agent for treating or preventing arteriosclerotic disease, which comprises any one of (a) to (c) as an active ingredient:
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(a) an oligonucleotide that hybridizes with a transcript of a PRKCH gene; (b) an antibody that recognizes a PRKCH protein; and (c) a mutant PRKCH protein which has an amino acid sequence in which valine at position 374 of the amino acid sequence of a PRKCH protein is substituted with isoleucine.
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- 27. A pharmaceutical agent for treating or preventing arteriosclerotic disease, which comprises as an active ingredient a substance that suppresses the expression of an AGTRL1 or PRKCH gene or suppresses the function of a protein encoded by said gene.
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30. A pharmaceutical agent for treating or preventing arteriosclerotic disease, which comprises as an active ingredient a substance that inhibits the binding of an Sp1 transcription factor with a DNA region that comprises a nucleotide site in the AGTRL1 gene located at position 39353 or 42509 of the nucleotide sequence of SEQ ID NO:
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31. A pharmaceutical agent for treating or preventing arteriosclerotic disease, which comprises as an active ingredient a substance that inhibits the autophosphorylation activity of a PRKCH protein.
- 32. A method of screening for a pharmaceutical agent for treating or preventing arteriosclerotic disease, which comprises selecting a compound that reduces the expression level of an AGTRL1 or PRKCH gene or reduces the activity of a protein encoded by said gene.
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33. A method of screening for a pharmaceutical agent for treating or preventing arteriosclerotic disease, which comprises the steps of:
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(a) contacting a test compound with a cell that expresses an AGTRL1 or PRKCH gene; (b) measuring the expression level of said AGTRL1 or PRKCH gene; and (c) selecting the compound that reduces the expression level as compared with that measured in the absence of the test compound.
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34. A method of screening for a pharmaceutical agent for treating or preventing arteriosclerotic disease, which comprises the steps of:
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(a) contacting a test compound with a cell or cell extract that comprises a DNA having a structure in which a transcriptional regulatory region of an AGTRL1 or PRKCH gene and a reporter gene are operably linked with each other; (b) measuring the expression level of said reporter gene; and (c) selecting a compound that reduces said expression level as compared with that measured in the absence of the test compound.
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36. A method of screening for a pharmaceutical agent for treating or preventing arteriosclerotic disease, which comprises the steps of:
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(a) contacting a test compound with an Sp1 transcription factor and a polynucleotide comprising a DNA region that comprises a nucleotide site in an AGTRL1 gene located at position 39353 or 42509 of the nucleotide sequence of SEQ ID NO;
1;(b) measuring the binding activity between said polynucleotide and the Sp1 transcription factor; and (c) selecting a compound that reduces said binding activity as compared with that measured in the absence of the test compound.
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37. A method of screening for a pharmaceutical agent for treating or preventing arteriosclerotic disease, which comprises the steps of:
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(a) contacting a test compound with a PRKCH protein; (b) measuring the autophosphorylation activity of the PRKCH protein; and (c) selecting a compound that reduces the autophosphorylation activity as compared with that measured in the absence of the test compound. - View Dependent Claims (38)
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39. A method of screening for a pharmaceutical agent for treating or preventing arteriosclerotic disease, which comprises the steps of:
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(a) contacting a test compound with a PRKCH protein; (b) measuring the protein kinase activity of the PRKCH protein; and (c) selecting a compound that reduces the protein kinase activity as compared with that measured in the absence of the test compound.
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Specification