WO1997039147B1 - Methods of identifying and diagnosing inflammatory bowel disease - Google Patents
Methods of identifying and diagnosing inflammatory bowel diseaseInfo
- Publication number
- WO1997039147B1 WO1997039147B1 PCT/US1997/006039 US9706039W WO9739147B1 WO 1997039147 B1 WO1997039147 B1 WO 1997039147B1 US 9706039 W US9706039 W US 9706039W WO 9739147 B1 WO9739147 B1 WO 9739147B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- tnf
- polymorphism
- locus
- nucleic acid
- ibd
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
Abstract
The present invention provides methods of identifying, diagnosing and screening for inflammatory bowel disease, particularly Crohn's Disease (CD) comprising identifying alleles and polymorphisms associated with a biological response related to an inflammatory bowel disease. The invention further provides for a method of determining whether a therapy which decreases the levels of TNF-α would be effective in treating an inflammatory bowel disease. The invention also provides for an assay system for screening for susceptibility to inflammatory bowel disease.
Claims
1. A method of identifying an mflammatory bowel disease (IBD) or subtype thereof, comprising selecting a population comprised of subjects having at least one biological response associated with IBD or a subtype thereof; obtaining nucleic acid from the subjects in the selected population; detecting a polymorphism at a functional site of a tumor necrosis factor (TNF) locus in the nucleic acid from the subjects; establishing whether a statistically significant correlation exists between the thus found polymorphism and at least one of the biological responses; and identifying an IBD or subtype thereof when the existence of a statistically significant correlation is established.
2. A method of diagnosing an inflammatory bowel disease (IBD) or subtype thereof, comprising selecting a subject exhibiting at least one biological response associated with IBD of subtype thereof; detecting a polymorphism at a functional site of a tumor necrosis factor (TNF) locus in the nucleic acid from the subject; comparing the found polymorphism with that of IBD or subtype DNA controls found by the method of claim 1 to have a statistically significant correlation with a biological response; and diagnosing IBD or a subtype thereof when a match with an IBD or subtype control is found.
3. A method of screening a population for susceptibility to inflammatory bowel disease (IBD) or subtype thereof, comprising diagnosing IBD or subtype thereof by applying the method of claim 2 to nucleic acid obtained from members of a predetermined population; and selecting the members of the population which show a statistically significant correlation with the biological response as exhibiting a susceptibility to IBD or subtype thereof.
4. The method of claim 1 , wherein the polymorphism comprises a mutation selected from the group consisting of nucleotide substitutions, additions, deletions and combination thereof.
5. The method of claim 4, wherein the polymorphism comprises a nucleotide substitution; and the nucleotide substitution comprises a substitution in the 5 ' regulatory region of a TNF-α locus.
6. The method of claim 5, wherein the nucleotide substitution in the TNF-α locus 5' regulatory region is selected from the group consisting of guanosine nucleotide substitutions at positions -238 and -308.
7. A method of identifying Crohn's Disease, comprising the method of claim 1, wherein the IBD comprises Crohn's Disease.
8. The method of claim 1, wherein the TNF locus comprises a TNF-α locus.
9. The method of claim 1 , wherein the biological response comprises an increase in the expression of the TNF-α gene with respect to a general population, as measured by TNF-α protein production or blood levels .
10. The method of claim 1, wherein the polymorphism is detected by isolating a fragment of the nucleic acid comprising the TNF locus from the sample; contacting the nucleic acid fragment with a TNF polymorphism-specific oligonucleotide probe under conditions effective to hybridize the nucleic acid and the polymorphism- specific oligonucleotide probe; detecting the presence of any hybrid formed; and taking the presence of any hybrid as an indication of the existence of a polymorphism.
11. The method of claim 10, wherein the nucleic acid is isolated by enzymatic amplification.
12. The method of claim 10, wherein the TNF polymorphism-specific probe comprises a TNF locus 5' regulatory region oligonucleotide selected from the group of oligonucleotides comprising residue -238 and oligonucleotides complementary thereto.
13. The method of claim 10, wherein the TNF polymorphism-specific probe comprises a TNF locus 5 ' regulatory region oligonucleotide selected from the group consisting of oligonucleotides comprising residue -308 and oligonucleotides complementary thereto.
14. The method of claim 10, further comprising enzymatically restricting the nucleic acid.
15. A method of diagnosing a susceptibility to Crohn's Disease (CD) in a subject, comprising identifying a polymorphism in a subject's DNA at a 5' regulatory region of a tumor necrosis factor-α (TNF-α) locus selected from the group consisting of positions -238 and -308; and diagnosing the subject as having a susceptibility to CD if either position comprises a guanosine nucleotide substitution.
16. A method of deteimiriing the effectiveness of a therapy to decrease the serum level of tumor necrosis factor-α (TNF-α) for treating inflammatory bowel disease, comprising detecting a polymorphism at a functional site within a TNF-α locus in a nucleic acid from a subject; and determining that the therapy is effective using the correlation found by the method of claim 1 with respect to TNF-α blood levels, if the TNF-α blood level is decreased and no longer exhibits a statistically significant correlation with the polymorphism.
17. The method of claim 16, wherein the inflammatory bowel disease comprises Crohn's Disease.
18. The method of claim 16, wherein the TNF locus polymorphism comprises a mutation selected from the group consisting of nucleotide substitutions, additions, deletions and combinations thereof.
19. The method of claim 18, wherein the mutation comprises a nucleotide substitution; and the nucleotide substitution comprises a substitution in the 5 ' regulatory region of a TNF-α locus.
20. The method of claim 19, wherein the nucleotide substitution in 5' regulatory region of the TNF-α locus is selected from the group consisting of a guanosine substitution at position -238 and -308.
21. An inflammatory bowel disease kit, comprising a nucleic acid comprising a DNA selected from the group consisting of those encoding a 5' regulatory region of a TNF-α locus comprising position -238 and complementary sequences thereto; and instructions for its use.
22. The kit of claim 21 , further comprising means for amplifying the nucleic acid.
23. The kit of claim 21, wherein the DNA is about 10 to 30 nucleotide long.
24. An inflammatory bowel disease kit, comprising a nucleic acid comprising a DNA selected from the group consisting of those encoding a 5 ' regulatory region of a TNF-α locus comprising position -308 and complementary sequences thereto; and instructions for its use.
25. The kit of claim 24, further comprising means for amplifying the nucleic acid.
26. The kit of claim 24, wherein the DNA is about 10 to 30 nucleotide long.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU24561/97A AU2456197A (en) | 1996-04-12 | 1997-04-11 | Methods of identifying and diagnosing inflammatory bowel disease |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US63067096A | 1996-04-12 | 1996-04-12 | |
| US08/630,670 | 1996-04-12 | ||
| US69836196A | 1996-08-15 | 1996-08-15 | |
| US08/698,361 | 1996-08-15 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1997039147A1 WO1997039147A1 (en) | 1997-10-23 |
| WO1997039147B1 true WO1997039147B1 (en) | 1997-12-11 |
Family
ID=27091205
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1997/006039 Ceased WO1997039147A1 (en) | 1996-04-12 | 1997-04-11 | Methods of identifying and diagnosing inflammatory bowel disease |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU2456197A (en) |
| WO (1) | WO1997039147A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2336431B (en) * | 1998-04-17 | 2003-06-25 | Johnson & Johnson Medical Ltd | Method of analysis of chronic wounds |
| GB0124315D0 (en) * | 2001-10-10 | 2001-11-28 | Oxagen Ltd | Inflammatory bowel disease |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2190586A1 (en) * | 1994-05-17 | 1995-11-23 | Scott E. Plevy | Methods of screening for crohn's disease using tnf microsatellite alleles |
-
1997
- 1997-04-11 AU AU24561/97A patent/AU2456197A/en not_active Abandoned
- 1997-04-11 WO PCT/US1997/006039 patent/WO1997039147A1/en not_active Ceased
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