Project 179111

This study will evaluate the effectiveness of vitamin D supplementation to enhance immune resistance to Mycobacterium tuberculosis (MTB) in a northern Dené community where tuberculosis rates exceed 600-900/100,000 - one of the highest rates in the world. The Dené in Manitoba are research partners with the University of Manitoba investigating the environmental, genetic and cultural factors that may be influencing the high rates of disease. A Dené Elder identified the loss of their traditional diet (caribou and fish) and the use of store foods as a cause of tuberculosis. Interestingly, before the use of antimicrobials to fight tuberculosis, the treatment was rest; exposure to sunlight and a diet rich in proteins, calories and nutrients including vitamin D. New research has investigated the role of vitamin D in the human immune response to infectious diseases and identified its downstream antimicrobial effect in cells infected with the tuberculosis bacilli. In our genetic analysis of a Dené and Cree cohort these groups were found to maintain a high frequency of genetic changes in the vitamin D receptor (VDR) genes which result in the weak transcription of this gene which in turn, may inhibit the optimal functioning of cells in the presence of MTB. We hypothesize therefore that the innate ability of cells to contain or eradicate MTB is compromised in the Dene population due to vitamin D deficiency (a long-standing health concern for northern populations) and the high frequency of functional genetic changes associated with the low expression of VDR. The objectives in this study will be to document and determine the prevalence of vitamin D deficiency in the Dené and determine whether or not vitamin D supplementation can overcome the effect of the gene changes associated with low expression of VDR, which is common among the Dene.