Contact: Joanne Stempak, Project Manager
416-586-4800 ext 8399
jstempak@mtsinai.on.ca

Primary Investigator: Mark Silverberg, MD
Enrolment: Ongoing
Sponsor: This initiative is funded by the National Institutes of Health in the United States and has allowed us to form an IBD Genetic Research Centre in order to build upon our previous efforts in this area.
Objective: Objective is to identify new genes and other biomarkers that may be responsible for causing Inflammatory Bowel Disease (IBD) and understand the role of previously identified biomarkers in IBD.

Expectation: This research will lead to a better understanding of why the disease occurs, easier diagnostic tools that may avoid the need for colonoscopies, better therapies or even a cure.

Eligibility: Anyone who has a confirmed diagnosis of IBD (either Crohn's Disease or Ulcerative Colitis). Also, if you do not have IBD (i.e. Crohn's Disease or ulcerative colitis) and do not have a family history of IBD and are willing to provide a blood sample as a healthy control, your help would be greatly appreciated.

Participation:

• Participation is very brief and involves providing us with:
  • Information regarding your family history and disease specifics
  • A small blood sample for genetic testing
  • Permission to review your medical information regarding IBD
• You will not have to see any physicians at Mount Sinai Hospital

Notes:

• Those with a family history of IBD may be asked for permission to contact affected individuals to participate as well.
• Those without a family history may also be asked for permission to contact parents or other unaffected relatives (even if they do NOT have IBD) to provide a blood sample.

Status Update:

Updated as of Fall 2011 by Joanne Stempak

Participant Tally:
5500 - this includes Crohn’s Disease and Ulcerative colitis patients, parents, siblings, other relatives, and non-IBD (healthy) controls.

We would like to sincerely thank all of our study participants. This research couldn't be possible without your cooperation.
Please contact Joanne Stempak as soon as possible if any of the following applies to you:

Parents:
It is extremely helpful to have parents participate in the study. If your parents have not yet sent in their consent forms and/or had their blood drawn, please remind them or contact us to help arrange this.

Relatives and Friends:
In some situations, we may have asked for your relatives, spouses/partners or friends to participate. This is important to complete your participation and to allow us to conduct this research.

Healthy Controls:
If you do not have IBD (i.e. Crohn's Disease or ulcerative colitis) and do not have a family history of IBD and are willing to provide a blood sample for this research, your help would be greatly appreciated.

Genetic Analysis / Results:
We are working with the samples that we have collected. This process takes a while and is ongoing. New findings are published in scientific research articles that are publicly available (link below). Below are the titles of some the research articles we have contributed to in this area.

Sub-studies:
a. Genetic Analysis of Infliximab-treated Inflammatory Bowel Disease Patients
Tumour necrosis factor-alpha blocking agents encompass some of the available therapies for Inflammatory Bowel Disease patients. Infliximab is one of the most popular and effective amongst them and is used in both Crohn’s Disease and Ulcerative colitis. Studies show that the majority of Inflammatory Bowel Disease patients undergoing Infliximab therapy experience beneficial effects from the drug. Nevertheless, a small number of patients experience moderate to severe adverse effects to Infliximab infusions. The potential risk for patients and the high cost of Infliximab therapy demand further research into the factors pertaining to therapy response. To date, there are no reliable predictors of Infliximab therapy outcome. With this study, we aim to identify differentially expressed genes between responders and non-responders to Infliximab therapy and to examine if significant gene expression differences exist between Infliximab-treated Ulcerative colitis and Crohn’s Disease patients.

We are looking for individuals who have Crohn’s Disease or Ulcerative colitis who will be starting Infliximab treatment in the near future. For this study, please contact Joanne Stempak or Tsedey Legesse (phone: 416-586-4800 x 4172).

b. Mechanisms of Intestinal Inflammation Following Ileal Resection for Crohn's Disease
For many Crohn's Disease patients with small portions of severely affected terminal ileum, surgical removal of the diseased bowel and reconnection of the two ends is considered a reasonable treatment option. However, patients may experience recurrence of their disease in the future following surgery. Similar to hypotheses regarding the development of Crohn’s Disease, those relating to the recurrence of inflammation following surgery suggest that inflammation is the result of altered immunity in genetically predisposed individuals due to a combination of changes in gene expression and the microbial milieu. The aim of this study is to evaluate microbial and gene expression factors which are associated with the recurrence of small bowel inflammation following surgery for CD. This will have practical implications for evaluating which patients are more likely to rapidly recur as well as provide insight into the pathogenesis of Crohn’s Disease.

We are looking for individuals who have Crohn’s Disease and are planning to undergo Ileal Resection. For this study, please contact Joanne Stempak or Tsedey Legesse  (phone: 416-586-4800 x 4172).

Articles:
Click on the underlined links to read the abstract summaries.

1. Muise AM, Walters T, Wine E, Griffiths AM, Turner D, Duerr RH, Regueiro MD, Ngan BY, Xu W, Sherman PM, Silverberg MS, Rotin D. Protein-tyrosine phosphatase sigma is associated with ulcerative colitis. Curr Biol. 2007 Jul 17;17(14):1212-8. Epub 2007 Jul 5.
2. De Jager PL, Franchimont D, Waliszewska A, Bitton A, Cohen A, Langelier D, Belaiche J, Vermeire S, Farwell L, Goris A, Libioulle C, Jani N, Dassopoulos T, Bromfield GP, Dubois B, Cho JH, Brant SR, Duerr RH, Yang H, Rotter JI, Silverberg MS, Steinhart AH, Daly MJ, Podolsky DK, Louis E, Hafler DA, Rioux JD; Quebec IBD Genetics Consortium; NIDDK IBD Genetics Consortium. The role of the Toll receptor pathway in susceptibility to inflammatory bowel diseases. Genes Immun. 2007 Jul;8(5):387-97. Epub 2007 May 31.
3. Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, Green T, Kuballa P, Barmada MM, Datta LW, Shugart YY, Griffiths AM, Targan SR, Ippoliti AF, Bernard EJ, Mei L, Nicolae DL, Regueiro M, Schumm LP, Steinhart AH, Rotter JI, Duerr RH, Cho JH, Daly MJ, Brant SR. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet. 2007 May;39(5):596-604. Epub 2007 Apr 15.
4. Dassopoulos T, Nguyen GC, Bitton A, Bromfield GP, Schumm LP, Wu Y, Elkadri A, Regueiro M, Siemanowski B, Torres EA, Gregory FJ, Kane SV, Harrell LE, Franchimont D, Achkar JP, Griffiths A, Brant SR, Rioux JD, Taylor KD, Duerr RH, Silverberg MS, Cho JH, Steinhart AH. Assessment of reliability and validity of IBD phenotyping within the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) IBD Genetics Consortium (IBDGC). Inflamm Bowel Dis. 2007 Aug;13(8):975-83.
5. Lal S, Appelton J, Mascarenhas J, Stempak JM, Esplen MJ, Silverberg MS. Attitudes toward genetic testing in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2007 Apr;19(4):321-7.
6. Hugot JP, Zaccaria I, Cavanaugh J, Yang H, Vermeire S, Lappalainen M, Schreiber S, Annese V, Jewell DP, Fowler EV, Brant SR, Silverberg MS, Cho J, Rioux JD, Satsangi J, Parkes M; for the IBD International Genetics Consortium. Prevalence of CARD15/NOD2 mutations in Caucasian healthy people. Am J Gastroenterol. 2007 Jun;102(6):1259-67. Epub 2007 Feb 23.
7. Silverberg MS, Duerr RH, Brant SR, Bromfield G, Datta LW, Jani N, Kane SV, Rotter JI, Philip Schumm L, Hillary Steinhart A, Taylor KD, Yang H, Cho JH, Rioux JD, Daly MJ; NIDDK IBD Genetics Consortium. Refined genomic localization and ethnic differences observed for the IBD5 association with Crohn's disease. Eur J Hum Genet. 2007 Mar;15(3):328-35. Epub 2007 Jan 10.
8. van Bodegraven AA, Curley CR, Hunt KA, Monsuur AJ, Linskens RK, Onnie CM, Crusius JB, Annese V, Latiano A, Silverberg MS, Bitton A, Fisher SA, Steinhart AH, Forbes A, Sanderson J, Prescott NJ, Strachan DP, Playford RJ, Mathew CG, Wijmenga C, Daly MJ, Rioux JD, van Heel DA. Genetic variation in myosin IXB is associated with ulcerative colitis. Gastroenterology. 2006 Dec;131(6):1768-74. Epub 2006 Sep 8.
9. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006 Dec 1;314(5804):1461-3. Epub 2006 Oct 26.
10. Lal S, Stempak JM, Law C, Elkadri AA, Steinhart AH, Silverberg MS. Association between the C3435T polymorphism of the MDR1 gene and Crohn's disease. Inflamm Bowel Dis. 2006 Oct;12(10):1006-7. No abstract available.
11. Nguyen GC, Torres EA, Regueiro M, Bromfield G, Bitton A, Stempak J, Dassopoulos T, Schumm P, Gregory FJ, Griffiths AM, Hanauer SB, Hanson J, Harris ML, Kane SV, Orkwis HK, Lahaie R, Oliva-Hemker M, Pare P, Wild GE, Rioux JD, Yang H, Duerr RH, Cho JH, Steinhart AH, Brant SR, Silverberg MS. Inflammatory bowel disease characteristics among African Americans, Hispanics, and non-Hispanic Whites: characterization of a large North American cohort. Am J Gastroenterol. 2006 May;101(5):1012-23.
12. Achkar JP, Dassopoulos T, Silverberg MS, Tuvlin JA, Duerr RH, Brant SR, Siminovitch K, Reddy D, Datta LW, Bayless TM, Zhang L, Barmada MM, Rioux JD, Steinhart AH, McLeod RS, Griffiths AM, Cohen Z, Yang H, Bromfield GP, Schumm P, Hanauer SB, Cho JH, Nicolae DL. Phenotype-stratified genetic linkage study demonstrates that IBD2 is an extensive ulcerative colitis locus. Am J Gastroenterol. 2006 Mar;101(3):572-80.

Links:

Entrez PubMed (a database of research articles): You can type in keywords (e.g. genetics and Inflammatory Bowel Disease) and generate a list of research articles in this area.

Dr. Mark Silverberg's Publications: This link lists research articles Dr. Silverberg has published.