التفاصيل البيبلوغرافية
| العنوان: |
DOPAMINE-BETA-HYDROXYLASE GENETIC POLYMORPHISM AND MIGRAINE |
| Document Number: |
20120004266 |
| تاريخ النشر: |
January 5, 2012 |
| Appl. No: |
12/999707 |
| Application Filed: |
June 18, 2008 |
| مستخلص: |
The invention provides a method of determining whether or not an individual has a predisposition to migraine including the step of determining whether an isolated nucleic acid obtained from the individual comprises a nucleotide sequence corresponding to at least a fragment of a dopamine β-hydroxylase (DBH) gene promoter, wherein the presence of a −1021C→T single nucleotide polymorphism (SNP) in said nucleotide sequence indicates whether or not said individual has an increased predisposition to migraine compared to an individual without the polymorphism. DBH −1021C/C homozygotes are particularly susceptible to migraine. The −1021T allele may exert a protective effect. The method is particularly suited to detection of a predisposition to migraine with aura in females. The invention also provides a diagnostic kit for detecting a −1021C→T SNP associated with migraine. The method and kit may facilitate selection of individuals for migraine therapy which targets the dopaminergic system. |
| Inventors: |
Griffiths, Lynette Robyn (Queensland, AU); Lea, Rod A. (Wellington, NZ); Fernandez, Francesca (Singapore, SG) |
| Assignees: |
Griffith University (Queensland, AU) |
| Claim: |
1. A method of determining whether or not an individual has a predisposition to migraine including the step of determining whether an isolated nucleic acid obtained from said individual comprises a nucleotide sequence corresponding to at least a fragment of a dopamine β-hydroxylase (DBH) gene promoter, wherein a single nucleotide polymorphism (SNP) in said nucleotide sequence indicates whether or not said individual has a predisposition to migraine. |
| Claim: |
2. The method of claim 1, wherein the SNP is at a position corresponding to nucleotide −1021 of a human DBH gene. |
| Claim: |
3. The method of claim 2, wherein the SNP comprises a cytosine at position −1021 which indicates that said individual has a predisposition to migraine. |
| Claim: |
4. The method of claim 3, wherein the individual is a homozygote. |
| Claim: |
5. The method of claim 2, wherein the SNP comprises a thymine at position −1021 which indicates that said individual does not have a predisposition to migraine or has a reduced likelihood of suffering from migraine. |
| Claim: |
6. The method of claim 5, wherein the individual is a homoozygote. |
| Claim: |
7. The method of claim 1, wherein the isolated nucleic acid is an amplification fragment obtained from said individual by PCR. |
| Claim: |
8. The method of claim 7, wherein PCR is performed using primers that respectively comprise a nucleotide sequence according to SEQ ID NO:1 and SEQ ID NO:2. |
| Claim: |
9. The method of claim 7, wherein said amplification fragment is subjected to restriction endonuclease digestion. |
| Claim: |
10. The method of claim 9, wherein restriction endonuclease digestion is performed using HhaI restriction endonuclease. |
| Claim: |
11. The method of claim 1, further including the step of measuring a level of DBH protein and/or DBH enzymatic activity, wherein a relatively reduced level and/or activity is indicative of a predisposition to migraine. |
| Claim: |
12. The method of claim 1, wherein migraine is migraine with aura (MA). |
| Claim: |
13. The method of claim 1, wherein the individual is a female human. |
| Claim: |
14. The method of claim 1, wherein said SNP indicates whether or not said individual has a predisposition to one or more migraine symptoms selected from emesis and diarrhea, or is less likely to display one or more migraine-associated symptoms selected from emesis and diarrhea. |
| Claim: |
15. The method of claim 1, which includes analysis of one or more gene sequence databases comprising genetic information obtained from said individual to thereby identify whether or not said individual has a predisposition to migraine. |
| Claim: |
16. A kit for use in the method of claim 1, said kit comprising one or more primers, probes and, optionally, one or more other reagents for identifying said SNP. |
| Claim: |
17. The kit of claim 16, which comprises one or more primers for nucleic acid sequence amplification of a nucleotide sequence corresponding to at least a fragment of a dopamine β hydroxylase gene promoter that comprises nucleotide −1021. |
| Claim: |
18. The kit of claim 17, wherein the primers comprise a nucleotide sequence according to SEQ ID NO:1 and SEQ ID NO:2. |
| Claim: |
19. The kit of claim 18, further comprising a restriction endonuclease. |
| Claim: |
20. The kit of claim 19, wherein the restriction endonuclease is HhaI. |
| Claim: |
21. A method of treating migraine including the steps of: (i) selecting an individual comprising a single nucleotide polymorphism (SNP) in a dopamine β-hydroxylase (DBH) gene promoter which is associated with a predisposition to migraine compared to an individual without the polymorphism; and (ii) treating the individual to thereby at least alleviate one or more symptoms of migraine. |
| Claim: |
22. The method of claim 21, wherein the SNP is at a position corresponding to −1021 of a human DBH gene. |
| Claim: |
23. The method of claim 22, wherein the SNP comprises a cytosine at position −1021. |
| Claim: |
24. The method of claim 23, wherein the individual is a homozygote. |
| Claim: |
25. The method of claim 21, further including the step of measuring a level of DBH protein and/or DBH enzymatic activity before step (ii), wherein a relatively reduced level and/or activity is indicative of a predisposition to migraine. |
| Claim: |
26. The method of claim 25, wherein step (ii) includes administering a dopamine receptor antagonist to the individual. |
| Claim: |
27. The method of claim 21, wherein migraine is migraine with aura (MA). |
| Claim: |
28. The method of claim 21, wherein the individual is a female human. |
| Current U.S. Class: |
514/327 |
| Current International Class: |
61; 61; 12 |
| رقم الانضمام: |
edspap.20120004266 |
| قاعدة البيانات: |
USPTO Patent Applications |
