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. 2008 Oct 15;198(8):1175-9.
doi: 10.1086/592049.

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

Linda A Larcombe  1 , Pamela H Orr, Andrew M Lodge, Jodie S Brown, Iga J Dembinski, Leisel C Milligan, Erin A Larcombe, Bruce D Martin, Peter W Nickerson
Affiliations

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

Linda A Larcombe et al. J Infect Dis. .

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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