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