1Department of Anthropology, University of Manitoba, 2Department of Internal Medicine, University of Manitoba, 3Department of Medical Microbiology, University of Manitoba, 4Department of Community Health Sciences, University of Manitoba, 5J.A. Hildes Northern Medical Unit, Department of Community Health Sciences, University of Manitoba
Saturday All day, Plaza Level
In Canada, there exists a large disparity in health status indicators between First Nation and non-First Nation populations. While socio-economic factors influence health, increased susceptibility to infectious disease has been associated with functional single nucleotide polymorphisms (SNPs) in promoter regions of cytokines and chemokines. With the support of First Nations communities, this study investigated immunogenetic variability and explored how genetics and the unique histories of these groups may contribute to differential resistance and/or susceptibility to infectious diseases.
DNA samples were collected from Dene, Saulteaux, Cree and Caucasian cohorts within the province of Manitoba. SNPs in Interleukin-12 (IL-12p40) promoter and in genes encoding the Toll-like Receptors 2 (TLR-2Arg753Gln) and 4 (TLR-4Asp299Gly,Thr399Ile) were typed using PCR-RFLP analysis. The relationships between ethnicity and SNP frequency were statistically examined.
Compared with the Caucasian and Saulteaux populations, the Dene and Cree were found to have a significantly higher frequency of SNPs associated with the low expression of IL-12, while variation within TLRs was not statistically significant. The lower production of the IL-12p40 subunit has been previously associated with the down-regulation of a Th-1 immune response-a response that is essential for the containment of Mycobacterium tuberculosis.
These results have identified variations in key immunological pathways between First Nations and Caucasians as well as within First Nation cohorts. The First Nations groups have unique cultural, political and historic identities and the contemporary immunogenetic profiles are likely a reflection of these histories. This, combined with socio-economic conditions, may be contributing to differential disease susceptibility.
This study was funded through Canadian Institutes of Health Research, the National Sanatorium Association and internal funds from the University of Manitoba.