Use of adamts4 gene and protein polymorphisms

A nucleic acid probe with the nucleic acid sequence according to SEQ ID No. 4, 7, 10 or 13.

A method for identifying cardiovascular and peripheral vascular disorders or an increased risk for developing cardiovascular and peripheral vascular disorders in an individual, which comprises examining a sample taken from an individual for the type of nucleotide which is present on one or more of the positions 635, 820, 835, 2564 and 10570 on one or both alleles of the ADAMTS4 gene, the type of nucleotide present at said one or more positions being indicative of the risk of said individual to suffer from or develop cardiovascular and peripheral vascular disorders.

A method for identifying cardiovascular and peripheral vascular disorders or an increased risk for developing cardiovascular and peripheral vascular disorders in an individual, which comprises examining a sample taken from an individual for the type of amino acid present at one or both of the positions 77 and 720 of the polypeptide chain of ADAMTS4 protein, the type of amino acid present at said one or more positions being indicative of the risk of said individual to suffer from or develop cardiovascular and peripheral vascular disorders.

A method for identifying cardiovascular and peripheral vascular disorders or an increased risk for developing cardiovascular and peripheral vascular disorders in an individual, which comprises examining a sample taken from an individual and determining the amount of ADAMTS4 mRNA present in said sample is different from that of one or more reference samples the presence of a different amount of ADAMTS4 mRNA indicating an increased risk to suffer from or develop cardiovascular and peripheral vascular disorders.

A method for identifying cardiovascular and peripheral vascular disorders or an increased risk for developing cardiovascular and peripheral vascular disorders in an individual, which comprises examining a sample taken from an individual and determining the amount of ADAMTS4 protein present in said sample is different from that of one or more reference samples the presence of a different amount of ADAMTS4 protein indicating an increased risk to suffer from or develop cardiovascular and peripheral vascular disorders.

A method of determining the risk of suffering from cardiovascular and peripheral vascular disorders comprising analysing an isolated sample of an individual for the type of nucleotide which is present on one or more of the positions 635, 820, 835, 2564 and 10570 on one or both alleles of the ADAMTS4 gene and calculating the estimated risk on basis of the age and the type of nucleotide present at one or more of the positions 635, 820, 835, 2564 and 10570 in the ADAMTS4 gene.

A method of determining the risk of suffering from cardiovascular and peripheral vascular disorders comprising analysing an isolated sample of an individual for the presence of one or more ADAMST4 protein polymorphisms and calculating the estimated risk on basis of the age and the type of amino acid present at position 77 or 720 of the ADAMTS4 protein.

A method for selecting a pharmaceutical or adapting the dosage of a pharmaceutical for the prevention and/or treatment of cardiovascular and peripheral vascular disorders in an individual, which comprises examining a taken sample of the individual for the type of the nucleotide which is present at one or more of the positions 635, 820, 835, 2564 and 10570 on either or both alleles of the ADAMTS4 gene, wherein said pharmaceutical being selected or said dosage being adapted is dependent of the type of nucleotide present at one or more of said positions.

A method for selecting a pharmaceutical or adapting the dosage of a pharmaceutical for the prevention and/or treatment of cardiovascular and peripheral vascular disorders in an individual, which comprises examining a taken sample of the individual for the type of amino acid present at one or both of the positions 77 and 720 in the amino acid chain of the ADAMTS4 protein, wherein said pharmaceutical being selected or said dosage being adapted is dependent of the type of amino acid present at one or both of said positions.

A method for selecting a pharmaceutical or adapting the dosage of a pharmaceutical for the prevention and/or treatment of cardiovascular and peripheral vascular disorders in an individual, which comprises examining a taken sample of the individual as to whether the amount of ADAMTS4 mRNA present in said sample is different from that of one or more taken reference samples said pharmaceutical being selected or said dosage being adapted depending on whether the amount of ADAMTS4 mRNA in the taken sample of the individual is different from that of the reference sample or reference samples.

A method for selecting a pharmaceutical or adapting the dosage of a pharmaceutical for the prevention and/or treatment of cardiovascular and peripheral vascular disorders in an individual, which comprises examining a taken sample of the individual as to whether the amount of ADAMTS4 protein present in said sample is different from that of one or more taken reference samples said pharmaceutical being selected or said dosage being adapted depending on whether the amount of ADAMTS4 protein in the taken sample of the individual is different from that of the reference sample or reference samples.

A method for identifying substances active in preventing or treating cardiovascular and peripheral vascular disorders comprising:

• a) contacting a ADAMTS4 protein or functional fragment or derivative thereof with a test substance;
• and
• b) determining whether the test substance modulates the activity of the ADAMTS4 protein or functional fragment or derivative thereof.

A method for identifying substances active in preventing or treating cardiovascular and peripheral vascular disorders comprising:

• a) contacting a cell, which has a detectable amount or activity of ADAMTS4 or of a functional fragment or derivative thereof, with a test substance;
• b) determining whether the test substance is able to modulate the amount or activity of ADAMTS4 or the functional fragment or derivative thereof present in the cell.

A test kit for diagnosing cardiovascular and peripheral vascular disorders or a predisposition for cardiovascular and peripheral vascular disorders, the test kit comprising at least one means for the detection of ADAMTS4 gene, mRNA or protein in one or more biological samples.

An isolated nucleic acid, having a genomic ADAMTS4 sequence according to SEQ ID No. 1 or 16 and comprising one or more single nucleotide polymorphisms (SNPs), the SNPs selected from the group consisting of an adenosine at position 635 of the genomic ADAMTS4 sequence, an adenosine at position 820 of the genomic ADAMTS4 sequence, a thymidine at position 835 of the genomic ADAMTS4 sequence, a guanosine at position 2564 of the genomic ADAMTS4 sequence and a guanosine at position 10570 of the genomic ADAMTS4 sequence.

An isolated ADAMTS4 protein having one or both protein polymorphisms selected from the group consisting of a threonine at position 77 of the polypeptide chain of the ADAMTS4 protein and an alanine at position 720 of the polypeptide chain of the ADAMTS4 protein.

The isolated ADAMTS4 protein according to claim 88 having the sequence selected from the group consisting of SEQ ID No. 3, 17, 18 and 19.

A nucleic acid primer with a nucleic acid sequence selected from the group consisting of SEQ ID No. 5, 6, 8, 9, 11, 12, 14 and 15.