Home

Health research with Manitoba First Nations. An investigation of gene variants affecting the Th17 immune pathway and the P2RX7 receptor.

Show simple item record

dc.contributor.supervisor Larcombe, Linda (Medical Microbiology) en_US
dc.contributor.author Semple, Catlin
dc.date.accessioned 2016-09-21T19:04:20Z
dc.date.available 2016-09-21T19:04:20Z
dc.date.issued 2016
dc.identifier.uri http://hdl.handle.net/1993/31848
dc.description.abstract Introduction: Canadian First Nations experience a significantly higher rate of Mycobacterium tuberculosis (MTB) infection than non-Indigenous Canadians. Th17 cells are a subset of CD4+ T cells that are distinguished by their production of Interleukin-17A (IL-17A), an important cytokine for defense against mycobacteria. IL-17 is a primary contributor to the formation and stabilization of the lung granuloma, a biological containment vessel to protect the host from tuberculosis (TB). Past research with First Nations people has identified single nucleotide polymorphisms (SNPs) in the Th1 and Th2 immune pathways may affect their disease risk. However, SNPs in key Th17 related genes and the P2RX7 gene have not been explored in First Nations despite their important role against infectious diseases. Hypothesis: This research hypothesizes that distinct First Nations groups (Dene, Cree and Saulteaux) will have a different frequencies of SNPs in the key Th17 immunity related genes (IL-17A, IL-17AR, IL-23R, and IFN-γR) and the P2RX7 gene, as compared to a non-Indigenous Canadian group. Methods: SNP profiles (IL-17A rs2275913, IL-17RA rs4819554, IL-23R rs10889677, IFN-γR rs2234711 and P2RX7 rs3751143) were identified through literature research and the NCBI database was used for identifying gene motifs, primer locations and Restriction Enzyme cut sites. Polymerase Chain Reaction and Restriction Fragment Length Polymorphism analysis was performed on and visualized on agarose gel to determine specific allele frequencies. Four different Manitoba First Nations communities; the Northern Dene (Dene 1 N=69. Dene 2 N=52), Central Cree (N=46), and Southern Saulteaux (N=56), participated in this research and their SNP profiles were compared to a non-Indigenous Canadian cohort (N=99). Results: Allele frequencies for IL-17A were statistically different for every First Nation community when compared to the non-Indigenous cohort (Dene 1 p=0.0043, Dene 2 p=0.0000, Cree p=0.0001, Saulteaux p=0.0000). Allele frequencies for IL-17RA were statistically different for every First Nation community except Saulteaux when compared to the non-Indigenous cohort (Dene 1 p=0.0000, Dene 2 p=0.0028, Cree p=0.0000). Allele frequencies for IL-23R were statistically different for Dene 1 and Saulteaux community when compared to the non-Indigenous cohort (Dene 1 p=0.0002, Saulteaux p=0.0000). Allele frequencies for IFN-R were statistically different for Cree community when compared to the non-Indigenous cohort (Cree p=0.0026). Allele frequencies for P2RX7 were statistically different for both Dene communities when compared to the non-Indigenous cohort (Dene 1 p=0.0000, Dene 2 p=0.0000). Conclusions: An effective Th17 response is required to bring Th1 cells to infected tissues and to balance inflammatory responses. Functional SNPs may compromise an appropriate immune response and contribute to disease. This study demonstrate that the non-Indigenous population maintained a significantly different genetic profile when compared to the First Nations populations. en_US
dc.subject First Nations en_US
dc.subject Indigenous en_US
dc.subject Interleukin-17 en_US
dc.subject Genetics en_US
dc.subject P2RX7 en_US
dc.subject IFN-gamma receptor en_US
dc.subject Interleukin-23 receptor en_US
dc.subject Immunogenetics en_US
dc.subject Tuberculosis en_US
dc.subject Knowledge translation en_US
dc.subject Interleukin-17 receptor en_US
dc.title Health research with Manitoba First Nations. An investigation of gene variants affecting the Th17 immune pathway and the P2RX7 receptor. en_US
dc.degree.discipline Medical Microbiology en_US
dc.contributor.examiningcommittee Fowke, Keith (Medical Microbiology) Mookherjee, Neeloffer (Immunology) en_US
dc.degree.level Master of Science (M.Sc.) en_US
dc.description.note October 2016 en_US


Files in this item

This item appears in the following Collection(s)

Show simple item record

View Statistics