Genetic polymorphisms associated with stroke, methods of detection and uses thereof
The present invention provides compositions and methods based on genetic polymorphisms that are associated with vascular diseases such as stroke. In particular, the present invention relates to genetic polymorphisms that have utility for such uses as predicting disease risk or predicting an individual's response to a treatment such as statins, including groups of polymorphisms that may be used as a signature marker set for such uses, as well as nucleic acid molecules containing the polymorphisms, variant proteins encoded by such nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and proteins, and methods of using the nucleic acid and proteins as well as methods of using reagents for their detection.
1. A method for treating noncardioembolic stroke in a human, the method comprising testing nucleic acid from said human for a polymorphism rs10757274 comprising G at position 101 of SEQ ID NO:1566 or C at its complement, detecting a homozygous genotype of said G or said C to thereby identify said human as having an increased risk for noncardioembolic stroke relative to not having said homozygous genotype, and administering a statin to treat noncardioembolic stroke to said human.
2. The method of claim 1 , wherein said testing comprises amplifying by polymerase chain reaction (PCR) a fragment of said nucleic acid that includes said polymorphism rs10757274 to thereby create an amplicon containing said polymorphism rs10757274.
3. The method of claim 1 , wherein said testing comprises sequencing said nucleic acid.
4. The method of claim 1 , wherein said testing comprises contacting said nucleic acid with an oligonucleotide that specifically hybridizes to said G or said C.
5. The method of claim 4 , wherein the nucleotide sequence of said oligonucleotide consists of a segment of at least 12 contiguous nucleotides of SEQ ID NO:1566 or its complement and includes said position 101.
6. The method of claim 4 , wherein said oligonucleotide is detectably labeled with a fluorescent dye.
7. The method of claim 4 , wherein said oligonucleotide is an allele-specific probe.
8. The method of claim 4 , wherein said oligonucleotide is an allele-specific primer.
9. The method of claim 8 , wherein said allele-specific primer comprises the nucleotide sequence of SEQ ID NO:1757.
10. A method for treating noncardioembolic stroke in a human, the method comprising testing nucleic acid from said human for a polymorphism rs10757274 comprising G at position 101 of SEQ ID NO:1566 or C at its complement, detecting a heterozygous genotype of said G or said C to thereby identify said human as having an increased responsiveness to statin treatment for reducing stroke risk relative to not having said heterozygous genotype, and administering a statin to treat noncardioembolic stroke to said human.
11. The method of claim 10 , wherein said testing comprises amplifying by polymerase chain reaction (PCR) a fragment of said nucleic acid that includes said polymorphism rs10757274 to thereby create an amplicon containing said polymorphism rs10757274.
12. The method of claim 10 , wherein said testing comprises sequencing said nucleic acid.
13. The method of claim 10 , wherein said testing comprises contacting said nucleic acid with an oligonucleotide that specifically hybridizes to said G or said C.
14. The method of claim 13 , wherein the nucleotide sequence of said oligonucleotide consists of a segment of at least 12 contiguous nucleotides of SEQ ID NO:1566 or its complement and includes said position 101.
15. The method of claim 13 , wherein said oligonucleotide is detectably labeled with a fluorescent dye.
16. The method of claim 13 , wherein said oligonucleotide is an allele-specific probe.
17. The method of claim 13 , wherein said oligonucleotide is an allele-specific primer.
18. The method of claim 17 , wherein said allele-specific primer comprises the nucleotide sequence of SEQ ID NO:1757.