Functional gene polymorphisms in canadian aboriginal populations with high rates of tuberculosis.
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.
Larcombe
Linda A
LA
Department of Medical Microbiology, University of Manitoba, Manitoba, Canada. larcombe@mts.net
Orr
Pamela H
PH
Lodge
Andrew M
AM
Brown
Jodie S
JS
Dembinski
Iga J
IJ
Milligan
Leisel C
LC
Larcombe
Erin A
EA
Martin
Bruce D
BD
Nickerson
Peter W
PW
D000328:Adult; D002170:Canada / Q000453:epidemiology / Q000208:ethnology; D016207:Cytokines / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics*; D014376:Tuberculosis / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D044465:White People
D016207:Cytokines; D018167:Receptors, Calcitriol