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Natural resistance-associated macrophage protein 1 polymorphisms are associated with microscopy-positive tuberculosis.

Abstract
The natural resistance-associated macrophage protein 1 (NRAMP1) is implicated in the pathophysiology of mycobacterial infections. We investigated by polymerase chain reaction previously published Nramp1 genotypes at 4 loci-INT4, N543D, 3'UTR, and 5'(CA)(n) microsatellite markers-in 104 human immunodeficiency virus-negative patients with tuberculosis and 176 healthy control subjects living in Denmark. No significant difference in genotype frequency was found between white patients with tuberculosis and control subjects (P>.16), but carriage of Nramp1 variant alleles at loci INT4 and 5'(CA)(n) conferred a significantly increased risk of having microscopy-positive compared with microscopy-negative tuberculosis (65% vs. 35% [P=.0004] and 63% vs. 38% [P=.047], respectively). The Nramp1 alleles were not associated with increased risk for the development of cavities seen on chest radiographs, or with extrapulmonary tuberculosis. These results indicate that variant alleles in the Nramp1 gene are associated with increased mycobacterial replication rather than susceptibility for tuberculosis and may thus confer increased risk of severe disease.
AuthorsChristian Søborg, Aase B Andersen, Hans O Madsen, Axel Kok-Jensen, Peter Skinhøj, Peter Garred
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 186 Issue 4 Pg. 517-21 (Aug 15 2002) ISSN: 0022-1899 [Print] United States
PMID12195379 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cation Transport Proteins
  • natural resistance-associated macrophage protein 1
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Asian People
  • Black People
  • Cation Transport Proteins (genetics)
  • Denmark (ethnology)
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genotype
  • Humans
  • Male
  • Microscopy (methods)
  • Middle Aged
  • Mycobacterium tuberculosis (isolation & purification)
  • Polymorphism, Genetic
  • Tuberculosis, Pulmonary (ethnology, genetics, microbiology)
  • White People

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