Methods of diagnosing ulcerative colitis and Crohn's disease

• US 5,681,699 A
• Filed: 02/11/1994
• Issued: 10/28/1997
• Est. Priority Date: 02/11/1994
• Status: Expired due to Term

• Current Assignee: Cedars-Sinai Medical Center (Cedars Sinai Health System)
• Original Assignee: Cedars-Sinai Medical Center (Cedars Sinai Health System)
• Inventors: Yang, Huiying, Targan, Stephan R., Rotter, Jerome I., Beaudet, Arthur L., Vora, Devendra
• Primary Examiner(s): Jones, W. Gary
• Assistant Examiner(s): WHISENANT, ETHAN C
• Application Number:
  US08/196,003
• Time in Patent Office: 1,355 Days
• Field of Search: 435/6, 536/23.1, 536/24.3
• US Class Current: 435/6.16
• CPC Class Codes: C07K 14/70525 ICAM molecules, e.g. CD50, CD54, CD102
• CPC Class Codes: C07K 16/2821 against ICAM molecules, e.g. CD50, CD54, CD102
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers

Abstract

A novel association between IBD and a polymorphism at amino acid residue 241 of ICAM-1 has been discovered. In accordance with the present invention there is provided methods of screening for IBD, methods for treating IBD, antibodies specifically reactive wish ICAM-1 encoded by R241 allele and kits which exploit the inventive methods.

Claims

1. A method of screening for inflammatory bowel disease ("IBD"), said method comprising;

a) obtaining a nucleic acid sample;

b) assaying the nucleic acid sample for the presence of a codon encoding arginine at amino acid position 241 of ICAM-1,

wherein the presence of a codon encoding arginine at amino acid position 241 of ICAM-1 is indicative of IBD.

2. A method in accordance with claim 1, wherein said IBD is ulcerative colitis ("UC").

3. A method in accordance with claim 1, wherein said IBD is Crohn'"'"'s disease ("CD").

4. A method in accordance with claim 1, wherein said assaying comprises amplification of the region of ICAM-1 containing nucleotide 721 of ICAM-1.

5. A method in accordance with claim 4, wherein said amplification comprises polymerase chain reaction using at least one primer selected from the group consisting of SEQ ID NO 4 and SEQ ID NO 5.

6. A method in accordance with claim 5, wherein said primer is SEQ ID NO 4.

7. A method in accordance with claim 5, wherein said primer is SEQ ID NO 5.

8. A method in accordance with claim 1, wherein said assaying comprises:

(a) contacting said nucleic acid with an allele-specific oligonucleotide probe under conditions suitable to cause the probe to hybridize with nucleic acid encoding R241 allele of the ICAM-1 gene, but not with nucleic acid encoding G241 allele of the ICAM-1 gene, and

(b) detecting the presence or absence of hybridization.

9. A method in accordance with claim 8, wherein said probe is about 7 to about 35 nucleotides in length.

10. A method in accordance with claim 8, wherein said probe comprises a sequence complementary to a region of genomic DNA encoding R241 allele wherein said region comprises at least the first nucleotide of codon 241.

11. A method in accordance with claim 8, wherein said probe comprises a sequence complementary to a region of SEQ ID NO 2, wherein said region comprises at least nucleotide 721 of SEQ ID NO 2.

12. A method in accordance with claim 1, wherein said assaying comprises:

(a) hybridizing said nucleic acid with a pair of oligonucleotide probes to produce a construct, wherein a first probe of said pair is labeled with a first label and a second probe of said pair is labeled with a second label, such that the first label is distinguishable from said second label, and the probes hybridize adjacent to each other at a nucleotide encoding amino acid residue 241 of ICAM-1;

(b) reacting said construct with a ligase in a reaction medium; and

then

(c) analyzing said reaction medium to detect the presence or absence of a ligation product comprising said first probe and said second probe.

13. A method in accordance with claim 1, further comprising detecting the presence or absence of anti-neutrophil cytoplasmic antibody in a sample of said subject.