title: Prevalence of genetic variants associated with inflammatory bowel disease in a healthy First Nations cohort.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Inflammatory Bowel Disease Group, Mount Sinai Hospital, University of Toronto, Toronto, Ont.
authors.forename: Travis B
authors.initials: TB
authors.lastname: Murdoch
authors.forename: Charles N
authors.initials: CN
authors.lastname: Bernstein
authors.forename: Hani
authors.initials: H
authors.lastname: El-Gabalawy
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Stempak
authors.forename: Michael
authors.initials: M
authors.lastname: Sargent
authors.forename: Brenda
authors.initials: B
authors.lastname: Elias
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Saad
authors.initials: S
authors.lastname: Pathan
authors.forename: Mark S
authors.initials: MS
authors.lastname: Silverberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007198:Indians, North American / Q000235:genetics* / Q000706:statistics & numerical data; D015212:Inflammatory Bowel Diseases / Q000453:epidemiology / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008350:Manitoba / Q000453:epidemiology; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data; D055815:Young Adult
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein