Prevalence of genetic variants associated with inflammatory bowel disease in a healthy First Nations cohort - 12/05/12
Contributors: Travis B. Murdoch, Charles N. Bernstein, Hani El-Gabalawy, Brenda Elias, Joanne M. Stempak, Saad Pathan and Mark S. Silverberg were involved in the study conception and design. Charles N. Bernstein, Hani El-Gabalawy, Michael Sargent, Joanne M. Stempak and Mark S. Silverberg were involved in the acquisition of data. Travis B. Murdoch, Charles N. Bernstein, Hani El-Gabalawy, Wei Xu and Mark S. Silverberg were involved in the analysis and interpretation of the data. Travis B. Murdoch wrote the manuscript, which was critically revised by all other authors. Charles N. Bernstein, Michael Sargent and Mark S. Silverberg provided technical and material support. Charles N. Bernstein, Hani El-Gabalawy and Mark S. Silverberg supervised the study. All of the authors approved the final version of the article submitted for publication.
Abstract |
Background |
Inflammatory bowel disease is the result of both genes and environment. Canadian First Nations people, despite living in a region with a high prevalence of inflammatory bowel disease, are relatively protected from this disease. We aimed to compare the carriage of genetic variants associated with inflammatory bowel disease in healthy First Nations and white people.
Methods |
DNA was extracted from the venous blood of healthy First Nations (n = 340) and white (n = 285) participants from Manitoba. Genotyping was performed for 69 single nucleotide polymorphisms (SNPs) with known or suspected associations with inflammatory bowel disease. We compared the genotypes between groups by logistic regression, adjusting for multiple testing. We calculated a risk score for the NOD2 gene by adding the number of risk alleles at three important NOD2 SNPs (G908R, R702W and 3020insC).
Results |
We found genetic variation between white and First Nations participants at 45 of 69 SNPs. Notably, carriage of the ATG16L1 T300A mutation was lower in First Nations participants (p = 4.1 × 10−30). Cumulative carriage of important NOD2 variants was significantly lower among First Nations participants (3.9% v. 15.2%; p < 0.0001 for risk score) than among white participants. Risk variants in IL23R (p = 0.014) and IL12B (p = 1.2 × 10−16), among others, were more prevalent among First Nations participants than among white participants.
Interpretation |
The low prevalence of variants associated with bacterial processing and handling in First Nations people may explain their relative protection from inflammatory bowel disease. Increased carriage of a number of risk variants, for example in the interleukin-23/Th17 pathway, is especially intriguing given their importance in other inflammatory diseases of high incidence in First Nations populations.
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| Funding: This work was funded by a Canadian Institutes for Health Research (CIHR) team grant on Arthritis and Inflammatory Bowel Disease. Dr. Bernstein is supported in part by the Bingham Chair in Gastroenterology. Dr. Silverberg is supported in part by the Gale and Graham Wright Research Chair in Digestive Diseases. Dr. Elias is supported in part by a CIHR New Investigator award. The study sponsors had no role in the design of the study, the collection, analysis or interpretation of data, the writing of the report or the decision to submit the article for publication. Competing interests: Charles N. Bernstein is on the advisory board of Abbott Canada, Janssen Canada and Shire Canada. He has served as a consultant for AstraZeneca Canada and has provided expert testimony for Ranbaxy Pharmaceuticals, Barr Pharmaceuticals, Cardinal Health and Mylan. He holds grants from Abbott Canada, Prometheus Laboratories and Aptalis and has received payment for lectures from Abbott Canada, Shire Canada and Merck Canada. Hani El-Gabalawy is on the advisory board for Roche, Bristol-Myers Squibb and Abbott. He holds grants from Roche, AstraZeneca, Abbott and Schering-Plough. He has given pharma-subsidized presentations at academic institutions and has received payment for the development of educational materials from Abbott and has received travel expenses for pharma-related talks. Mark Silverberg holds grants from the National Institute of Diabetes and Digestive and Kidney Diseases and the Crohn’s and Colitis Foundation of Canada. He is a member of the advisory board of and has served as a consultant for Abbott, Janssen and Prometheus Laboratories. He holds grants and has received payment for lectures from these companies. No competing interests declared for all other authors. This article has been peer reviewed. |
Vol 184 - N° 8
P. E435-E441 - mai 2012 Retour au numéro
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