Larcombe Linda A, Shafer Leigh Anne, Nickerson Peter W, Lodge Andrew M, Brown Jodie S, Milligan Leisel C, Pochinco Denise, Beaudin Lynnette, Arundel Brian, Wong Jacqueline, Dantouze Joe, Denechezhe Lizette, Orr Pamela H
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.
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.
Hum Immunol. 2017 May-Jun;78(5-6):401-411. doi: 10.1016/j.humimm.2017.03.009. Epub 2017 Mar 27.
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.
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.
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-A03 and HLA-DQB105:03 were significantly associated with TB.
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.
加拿大曼尼托巴省的原住民中，流行性和地方性结核病的发病率极高。调节人类白细胞抗原（HLA）I类和II类抗原的基因多态性是结核病的风险标志物之一，其他还包括生物和社会健康决定因素。对曼尼托巴省两个原住民群体的HLA - A、B、DRB1、DQA1、DQB1进行基因分型，以识别和比较可能影响结核病易感性或抵抗力的基因多态性频率。
自我认定为戴内人或克里人的参与者从加拿大曼尼托巴省的两个原住民社区招募进入本研究。在获得知情同意后，从戴内人（N = 63）和克里人（N = 42）原住民研究参与者采集的血样中提取基因组DNA。参与者自我报告曾接受过活动性结核病治疗、潜伏性结核病治疗或未患结核病。使用市售试剂盒中的序列特异性寡核苷酸（SSO）探针进行HLA I类和II类分子分型。
戴内人参与者中接受治疗的活动性和潜伏性结核病发病率略高于克里人参与者（p = 0.112）。I类和II类HLA基因座在戴内人和克里人群体中均处于哈迪-温伯格平衡。在对戴内人和克里人队列中的结核病与HLA等位基因频率进行的这项探索性分析中，HLA - A03和HLA - DQB105:03与结核病显著相关。
加拿大戴内人和克里人群体中结核病的高发病率需要生物医学和社会经济方面的预防及控制措施。在前者中，了解原住民群体中的HLA多样性可能有助于开发新的有效疫苗和治疗方法，这些方法依赖于小分子与特定HLA表位之间的相互作用。
