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

Larcombe, Linda A; Orr, Pamela H; Lodge, Andrew M; Brown, Jodie S; Dembinski, Iga J; Milligan, Leisel C; Larcombe, Erin A; Martin, Bruce D et al. · J Infect Dis · 2008

case_control · Level III

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Abstract

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. tuberculosis and the opposing role of MCP-1 and IL-6, the observed allelic variation by ethnicity may in part contribute to the high rates of tuberculosis among the Dené.

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