Linda A Larcombe1, Leigh Anne Shafer2, Peter W Nickerson3, Andrew M Lodge4, Jodie S Brown4, Leisel C Milligan5, Denise Pochinco6, Lynnette Beaudin7, Brian Arundel6, Jacqueline Wong7, Joe Dantouze8, Lizette Denechezhe8, Pamela H Orr9. 1. 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. 2. 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. 3. 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. 4. Rady Faculty of Health Sciences, Department of Internal Medicine, University of Manitoba, GC425, Health Sciences Centre, 820 Sherbrook St., Winnipeg, MB R3E 0W3, Canada. 5. Rady Faculty of Health Sciences, Department of Medical Microbiology, University of Manitoba, 745 Bannatyne Ave., Winnipeg, MB, Canada. 6. Transplant Immunology Laboratory, Diagnostic Services of Manitoba, 777 William Avenue, Winnipeg, Manitoba R3E 3R4, Canada. 7. Platelet Immunology Laboratory, Canadian Blood Services, 777 William Avenue, Winnipeg, Manitoba R3E 3R4, Canada. 8. Northlands Denesuline First Nation, Lac Brochet Manitoba, Canada. 9. 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.
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.
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: Chunxin Liao; Jiahui Yang; Jinli Wang; Xialin Du; Ruining Wang; Shimeng Zhang; Wenting He; Qian Wen; Li Ma Journal: Nan Fang Yi Ke Da Xue Xue Bao Date: 2018-01-30
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Authors: Aftab Alam; Hala Abubaker Bagabir; Armiya Sultan; Mohd Faizan Siddiqui; Nikhat Imam; Mustfa F Alkhanani; Ahmad Alsulimani; Shafiul Haque; Romana Ishrat Journal: Front Pharmacol Date: 2022-01-27 Impact factor: 5.810