HLA-A, B, DRB1, DQA1, DQB1 alleles and haplotype frequencies in Dene and Cree cohorts in Manitoba, Canada.

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.

Functional gene polymorphisms in canadian aboriginal populations with high rates of tuberculosis.

The present study determined whether a pattern of functional single-nucleotide polymorphisms (SNPs) was present that could predispose a Dené cohort to a suboptimal response to Mycobacterium tuberculosis. Compared with a Caucasian cohort, the Dené and Cree were found to maintain a significantly higher frequency of SNPs associated with low expression of vitamin D receptor (VDR), interferon (IFN)-gamma (+874), and tumor necrosis factor-alpha (-308) and high production of monocyte chemoattractant protein (MCP)-1 (-2518) and interleukin (IL)-6 (-174). Given the roles played by IFN-gamma and VDR in facilitating macrophage containment of M.