1. SLC11A1 (NRAMP1) but not SLC11A2 (NRAMP2) polymorphisms are associated with susceptibility to tuberculosis in a high-incidence community in South Africa.
- Author
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Hoal EG, Lewis LA, Jamieson SE, Tanzer F, Rossouw M, Victor T, Hillerman R, Beyers N, Blackwell JM, and Van Helden PD
- Subjects
- Adult, Case-Control Studies, Female, Genetic Predisposition to Disease, Humans, Incidence, Male, South Africa epidemiology, Cation Transport Proteins genetics, Iron-Binding Proteins genetics, Polymorphism, Genetic, Tuberculosis, Pulmonary epidemiology, Tuberculosis, Pulmonary genetics
- 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 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.
- Published
- 2004