SLC11A1 (NRAMP1) but not SLC11A2 (NRAMP2) polymorphisms are associated with susceptibility to tuberculosis in a high-incidence community in South Africa

Int J Tuberc Lung Dis. 2004 Dec;8(12):1464-71.


Setting: Stellenbosch University Faculty of Health Sciences, and metropolitan Cape Town, Western Cape, South Africa.

Objective: To investigate whether the reported association between SLC11A1 (also NRAMP1) polymorphisms and susceptibility to tuberculosis (TB) can be confirmed in a different population, and whether polymorphisms in SLC11A2 (also NRAMP2, DCT1, DMT1) are associated with TB.

Design: A case-control study design was used to compare the frequencies of five polymorphisms in SLC11A1 and three in SLC11A2 between a group of bacteriologically confirmed TB patients and healthy community controls.

Results: The 5' (GT)9 allele in the promoter of SLC1A1 was found at significantly higher frequencies among 265 controls than in 224 pulmonary TB (PTB) patients (P = 0.002; OR 0.6; 95% CI 0.43-0.83). Homozygotes for the TGTG deletion (1729+55del4) in the 3'UTR of SLC11A1 were over-represented among PTB patients (P = 0.013; OR 5.19; 95% CI 1.42-18.94). Stepwise logistic regression analysis indicated that the 5' and 3' polymorphisms contribute separate main effects. Tuberculous meningitis patients (n = 22) showed the same allele and genotype frequency as PTB patients. No SLC11A2 polymorphisms tested were associated with TB.

Conclusion: The 5' (GT)n allele driving the highest rate of transcription of SLC11A1 appears to be associated with protection against TB in the majority of the populations studied.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Cation Transport Proteins / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Incidence
  • Iron-Binding Proteins / genetics*
  • Male
  • Polymorphism, Genetic*
  • South Africa / epidemiology
  • Tuberculosis, Pulmonary / epidemiology*
  • Tuberculosis, Pulmonary / genetics*


  • Cation Transport Proteins
  • Iron-Binding Proteins
  • natural resistance-associated macrophage protein 1
  • solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2