Prevalence of genetic variants associated with inflammatory bowel disease in a healthy First Nations cohort

Travis B. Murdoch, Charles N. Bernstein, Hani El-Gabalawy, Joanne M. Stempak, Michael Sargent, Brenda Elias, Wei Xu, Saad Pathan, Mark S. Silverberg

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
JournalCMAJ
Volume184
Issue number8
DOIs
Publication statusPublished - 15 May 2012
Externally publishedYes

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Inflammatory Bowel Diseases
Single Nucleotide Polymorphism
Manitoba
Interleukin-23
Genes
Logistic Models
Alleles
Genotype
Mutation
DNA
Incidence
Population

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Murdoch, T. B., Bernstein, C. N., El-Gabalawy, H., Stempak, J. M., Sargent, M., Elias, B., ... Silverberg, M. S. (2012). Prevalence of genetic variants associated with inflammatory bowel disease in a healthy First Nations cohort. CMAJ, 184(8). https://doi.org/10.1503/cmaj.110613

Prevalence of genetic variants associated with inflammatory bowel disease in a healthy First Nations cohort. / Murdoch, Travis B.; Bernstein, Charles N.; El-Gabalawy, Hani; Stempak, Joanne M.; Sargent, Michael; Elias, Brenda; Xu, Wei; Pathan, Saad; Silverberg, Mark S.

In: CMAJ, Vol. 184, No. 8, 15.05.2012.

Research output: Contribution to journalArticle

Murdoch, TB, Bernstein, CN, El-Gabalawy, H, Stempak, JM, Sargent, M, Elias, B, Xu, W, Pathan, S & Silverberg, MS 2012, 'Prevalence of genetic variants associated with inflammatory bowel disease in a healthy First Nations cohort', CMAJ, vol. 184, no. 8. https://doi.org/10.1503/cmaj.110613
Murdoch TB, Bernstein CN, El-Gabalawy H, Stempak JM, Sargent M, Elias B et al. Prevalence of genetic variants associated with inflammatory bowel disease in a healthy First Nations cohort. CMAJ. 2012 May 15;184(8). https://doi.org/10.1503/cmaj.110613
Murdoch, Travis B. ; Bernstein, Charles N. ; El-Gabalawy, Hani ; Stempak, Joanne M. ; Sargent, Michael ; Elias, Brenda ; Xu, Wei ; Pathan, Saad ; Silverberg, Mark S. / Prevalence of genetic variants associated with inflammatory bowel disease in a healthy First Nations cohort. In: CMAJ. 2012 ; Vol. 184, No. 8.
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