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


METHODS
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.


CONCLUSIONS
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.
Hoal
E G
EG
Medical Biochemistry and MRC Centre for Molecular and Cellular Biology, Stellenbosch University, Tygerberg, South Africa. egvh@sun.ac.za
Lewis
L A
LA
Jamieson
S E
SE
Tanzer
F
F
Rossouw
M
M
Victor
T
T
Hillerman
R
R
Beyers
N
N
Blackwell
J M
JM
Van Helden
P D
PD
D000328:Adult; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D033862:Iron-Binding Proteins / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D013019:South Africa / Q000453:epidemiology; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology* / Q000235:genetics*; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2
D027682:Cation Transport Proteins; D033862:Iron-Binding Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2