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

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.