title: HLA-A, B, DRB1, DQA1, DQB1 alleles and haplotype frequencies in Dene and Cree cohorts in Manitoba, Canada.
abstract: BACKGROUND
  First Nations in the Canadian province of Manitoba have disproportionately high rates of epidemic and endemic TB. Gene polymorphisms that modulate HLA Class I and II antigens are among the risk markers for TB, along with other biologic, and social determinants of health. HLA-A, B, DRB1, DQA1, DQB1 were typed in two Manitoba First Nation indigenous groups to identify and compare the frequency of gene polymorphisms that may influence susceptibility or resistance to TB.
  
  
  METHODS
  Participants who self-identified as either Dene or Cree enrolled into the study from two First Nation communities in Manitoba, Canada. Genomic DNA was extracted from blood samples collected with informed consent from Dene (N=63) and Cree (N=42) First Nation study participants. Participants self-reported having treated active TB, treated latent TB or no TB. HLA Class I and II molecules were typed using sequence-specific oligonucleotide (SSO) probes from commercially available kits.
  
  
  RESULTS
  The rates of treated active and latent TB were marginally higher among the Dene than the Cree participants (p=0.112). Class I and II HLA loci were in Hardy-Weinberg equilibrium in both the Dene and Cree groups. In this exploratory analysis of TB and HLA allele frequencies in Dene and Cree cohorts HLA-A*03 and HLA-DQB1*05:03 were significantly associated with TB.
  
  
  CONCLUSIONS
  The high incidence of TB in both Dene and Cree populations in Canada requires both biomedical and socioeconomic prevention and control measures. Among the former, an understanding of HLA diversity among First Nations groups may aid the development of new effective vaccine and therapeutic modalities that depend on the interaction between small molecules and specific HLA epitopes.
authors.affiliation: Rady Faculty of Health Sciences, Department of Internal Medicine, University of Manitoba, GC425, Health Sciences Centre, 820 Sherbrook St., Winnipeg, MB R3E 0W3, Canada; Department of Anthropology, 435 Fletcher Argue Building, University of Manitoba, Winnipeg, Manitoba R3T 5V5, Canada; Rady Faculty of Health Sciences, Department of Medical Microbiology, University of Manitoba, 745 Bannatyne Ave., Winnipeg, MB, Canada; Rady Faculty of Health Sciences, Department of Community Health Sciences, University of Manitoba, T162-770 Bannatyne Ave., Winnipeg, Manitoba R3E 0W3, Canada. Electronic address: llarcombe@hsc.mb.ca.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Larcombe
authors.affiliation: Rady Faculty of Health Sciences, Department of Internal Medicine, University of Manitoba, GC425, Health Sciences Centre, 820 Sherbrook St., Winnipeg, MB R3E 0W3, Canada; Rady Faculty of Health Sciences, Department of Community Health Sciences, University of Manitoba, T162-770 Bannatyne Ave., Winnipeg, Manitoba R3E 0W3, Canada.
authors.forename: Leigh Anne
authors.initials: LA
authors.lastname: Shafer
authors.affiliation: Rady Faculty of Health Sciences, Department of Medical Microbiology, University of Manitoba, 745 Bannatyne Ave., Winnipeg, MB, Canada; Transplant Immunology Laboratory, Diagnostic Services of Manitoba, 777 William Avenue, Winnipeg, Manitoba R3E 3R4, Canada.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Nickerson
authors.affiliation: Rady Faculty of Health Sciences, Department of Internal Medicine, University of Manitoba, GC425, Health Sciences Centre, 820 Sherbrook St., Winnipeg, MB R3E 0W3, Canada.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lodge
authors.affiliation: Rady Faculty of Health Sciences, Department of Internal Medicine, University of Manitoba, GC425, Health Sciences Centre, 820 Sherbrook St., Winnipeg, MB R3E 0W3, Canada.
authors.forename: Jodie S
authors.initials: JS
authors.lastname: Brown
authors.affiliation: Rady Faculty of Health Sciences, Department of Medical Microbiology, University of Manitoba, 745 Bannatyne Ave., Winnipeg, MB, Canada.
authors.forename: Leisel C
authors.initials: LC
authors.lastname: Milligan
authors.affiliation: Transplant Immunology Laboratory, Diagnostic Services of Manitoba, 777 William Avenue, Winnipeg, Manitoba R3E 3R4, Canada.
authors.forename: Denise
authors.initials: D
authors.lastname: Pochinco
authors.affiliation: Platelet Immunology Laboratory, Canadian Blood Services, 777 William Avenue, Winnipeg, Manitoba R3E 3R4, Canada.
authors.forename: Lynnette
authors.initials: L
authors.lastname: Beaudin
authors.affiliation: Transplant Immunology Laboratory, Diagnostic Services of Manitoba, 777 William Avenue, Winnipeg, Manitoba R3E 3R4, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Arundel
authors.affiliation: Platelet Immunology Laboratory, Canadian Blood Services, 777 William Avenue, Winnipeg, Manitoba R3E 3R4, Canada.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Wong
authors.affiliation: Northlands Denesuline First Nation, Lac Brochet Manitoba, Canada.
authors.forename: Joe
authors.initials: J
authors.lastname: Dantouze
authors.affiliation: Northlands Denesuline First Nation, Lac Brochet Manitoba, Canada.
authors.forename: Lizette
authors.initials: L
authors.lastname: Denechezhe
authors.affiliation: Rady Faculty of Health Sciences, Department of Internal Medicine, University of Manitoba, GC425, Health Sciences Centre, 820 Sherbrook St., Winnipeg, MB R3E 0W3, Canada; Rady Faculty of Health Sciences, Department of Medical Microbiology, University of Manitoba, 745 Bannatyne Ave., Winnipeg, MB, Canada; Rady Faculty of Health Sciences, Department of Community Health Sciences, University of Manitoba, T162-770 Bannatyne Ave., Winnipeg, Manitoba R3E 0W3, Canada.
authors.forename: Pamela H
authors.initials: PH
authors.lastname: Orr
mesh_terms: D002170:Canada; D015331:Cohort Studies; D019353:Endemic Diseases; D005006:Ethnicity; D005787:Gene Frequency; D056726:Genetic Association Studies; D015791:HLA-A3 Antigen / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains / Q000235:genetics; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D055985:Latent Tuberculosis / Q000453:epidemiology*; D011110:Polymorphism, Genetic; D015995:Prevalence
chemical_list: C487960:HLA-A*03 antigen; D015791:HLA-A3 Antigen; D015235:HLA-B Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains
keywords: First Nations; Genetics; HLA; Immunity; TB