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

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Abstract:

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 SLC11A1 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.

Keywords: SLC11A1; SLC11A2; association; susceptibility; tuberculosis

Document Type: Regular Paper

Affiliations: 1: Medical Biochemistry and MRC Centre for Molecular and Cellular Biology, Stellenbosch University, Tygerberg, South Africa 2: Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, United Kingdom 3: Department of Genetics, Stellenbosch University, Tygerberg, South Africa 4: Department of Paediatrics and Child Health, Stellenbosch University, Tygerberg, South Africa

Publication date: December 1, 2004

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

    Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website

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