US2016090629A1PendingUtilityA1

Variants of tnfsf15 and dcr3 associated with crohn's disease

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Assignee: CEDARS SINAI MEDICAL CENTERPriority: May 17, 2013Filed: May 16, 2014Published: Mar 31, 2016
Est. expiryMay 17, 2033(~6.8 yrs left)· nominal 20-yr term from priority
Inventors:Dermot P. Mcgovern
A61P 43/00A61P 37/06A61P 29/00A61P 1/04C12Q 2600/156C12Q 2600/172C12Q 2600/112C12Q 1/6883C12Q 2600/118C07K 16/2875
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Claims

Abstract

Described herein are methods and compositions related to the discovery of associations in TNFSF15 15 and DcR3 genetic loci across in Caucasian, Puerto Rican, and Korean Crohn's Disease, as demonstrated via trans-ethnic fine mapping. The present invention provides methods of quantifying risk and diagnosing susceptibility to Crohn's disease in a subject by determining the presence of one or more risk variants are at the TNFSF15 (or TL1A) and/or DcR3 genetic loci.

Claims

exact text as granted — not AI-modified
1 . An assay for quantifying risk in a subject to Crohn's disease and/or fibrosis, comprising:
 obtaining a sample from a subject;   subjecting the sample to a genotyping assay adapted to determine the presence or absence of one or more variants at the TNFSF15 and/or DcR3 genetic loci; and   quantifying risk in a subject to Crohn's disease and/or fibrosis based on the presence of one or more variants at the TNFSF15 and/or DcR3genetic loci.   
     
     
         2 . The method of  claim 1 , wherein the variants consist of one or more variants selected from the group consisting of: SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5, SEQ ID NO. 6, SEQ ID NO. 7, SEQ ID NO. 8, SEQ ID NO. 9, SEQ ID NO. 10, SEQ ID NO. 11, SEQ ID NO. 12, SEQ ID NO. 13, SEQ ID NO. 14, SEQ ID NO. 15, SEQ ID NO. 16, SEQ ID NO. 17, SEQ ID NO. 18, SEQ ID NO. 19, SEQ ID NO. 20, SEQ ID NO. 21, SEQ ID NO. 22, SEQ ID NO. 23, SEQ ID NO. 24, SEQ ID NO. 25, and SEQ ID NO. 26. 
     
     
         3 . The method of  claim 1 , wherein the variants are SEQ ID NO. 3 and/or SEQ ID NO.13. 
     
     
         4 . The method of  claim 1 , wherein the variant is SEQ ID NO. 22. 
     
     
         5 . The method of  claim 1 , wherein the subject is non-Jewish Caucasian, Ashkenazi, South Korean and/or Puerto Rican. 
     
     
         6 . The method of  claim 1 , wherein the subject is South Korean and the variant are SEQ ID NO. 3, SEQ ID NO.13 and/or SEQ ID NO. 22. 
     
     
         7 . The method of  claim 1 , wherein the variant is a risk variant. 
     
     
         8 . The method of  claim 1 , wherein the variant is a protective variant. 
     
     
         9 . The method of  claim 1 , wherein the protective variant quantifies a reduced risk in the subject for stricturing, CD, small bowel involvement and/or need for surgical intervention. 
     
     
         10 . A method of diagnosing susceptibility to Crohn's disease and/or fibrosis in a subject, comprising:
 obtaining a sample from a subject;   subjecting the sample to a genotyping assay adapted to determine the presence or absence of one or more variants at the TNFSF15 and/or DcR3 genetic loci; and   diagnosing susceptibility to Crohn's disease and/or fibrosis in the subject based on the presence of one or more variants at the TNFSF15 and/or DcR3 genetic loci.   
     
     
         11 . The method of  claim 10 , wherein the variants consist of one or more variants selected from the group consisting of: SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5, SEQ ID NO. 6, SEQ ID NO. 7, SEQ ID NO. 8, SEQ ID NO. 9, SEQ ID NO. 10, SEQ ID NO. 11, SEQ ID NO. 12, SEQ ID NO. 13, SEQ ID NO. 14, SEQ ID NO. 15, SEQ ID NO. 16, SEQ ID NO. 17, SEQ ID NO. 18, SEQ ID NO. 19, SEQ ID NO. 20, SEQ ID NO. 21, SEQ ID NO. 22, SEQ ID NO. 23, SEQ ID NO. 24, SEQ ID NO. 25, and SEQ ID NO. 26. 
     
     
         12 . The method of  claim 10 , wherein the variants are SEQ ID NO. 3 and/or SEQ ID NO.13. 
     
     
         13 . The method of  claim 10 , wherein the variant is SEQ ID NO. 22. 
     
     
         14 . The method of  claim 10 , wherein the subject is non-Jewish Caucasian, Ashkenazi, South Korean and/or Puerto Rican. 
     
     
         15 . The method of  claim 10 , wherein the subject is South Korean and the variant are SEQ ID NO. 3, SEQ ID NO.13 and/or SEQ ID NO. 22. 
     
     
         16 . A method of treating Crohn's disease and/or fibrosis in a subject, comprising:
 obtaining a sample from the subject;   subjecting the sample to a genotyping assay adapted to determine the presence of one or more variants at the TNFSF15 and/or DcR3 genetic loci; and   treating the Crohn's disease and/or fibrosis.   
     
     
         17 . The method of  claim 16 , wherein the variants consist of one or more variants selected from the group consisting of: SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5, SEQ ID NO. 6, SEQ ID NO. 7, SEQ ID NO. 8, SEQ ID NO. 9, SEQ ID NO. 10, SEQ ID NO. 11, SEQ ID NO. 12, SEQ ID NO. 13, SEQ ID NO. 14, SEQ ID NO. 15, SEQ ID NO. 16, SEQ ID NO. 17, SEQ ID NO. 18, SEQ ID NO. 19, SEQ ID NO. 20, SEQ ID NO. 21, SEQ ID NO. 22, SEQ ID NO. 23, SEQ ID NO. 24, SEQ ID NO. 25, and SEQ ID NO. 26.

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