This finding, together with the emerging information on almost total sequence homology between the murine and human Nramp genes suggests that this gene may be responsible for the phenotype of resistance or susceptibility to tuberculosis.
To determine the model of inheritance for genetic susceptibility to tuberculosis, and to test the hypothesis that TNFA and NRAMP1 are candidate susceptibility genes.
Through comparative genomics, we have identified the homologous human NRAMP1 gene, alleles of which are now being used for tests of linkage with TB and leprosy.
Recent genetic studies have found that allelic variants at the human NRAMP1 locus are associated with susceptibility to leprosy (Mycobacterium leprae) and tuberculosis (Mycobacterium tuberculosis) and possibly with the onset of rheumatoid arthritis.
Several studies now provide evidence for a role for NRAMP1 in determining human susceptibility to autoimmune (rheumatoid arthritis. juvenile rheumatoid arthritis, diabetes, Crohn's disease) and infectious (tuberculosis, leprosy) diseases.Amongst these. data are accumulating to support the hypothesis that a functional Z-DNA forming repeat polymorphism in the promoter region of human NRAMP1 contributes directly to disease susceptibility.
For example, tumour necrosis factor polymorphisms have been associated with susceptibility to malaria and other infections; chemokine receptor polymorphisms with susceptibility to HIV; natural resistance-associated macrophage protein 1 with tuberculosis; and mannose binding lectin polymorphisms with meningococcal disease.
Whereas NRAMP1 polymorphisms have been associated with increased susceptibility to tuberculosis, our results suggest that at least one NRAMP1 polymorphism may decrease susceptibility in sarcoidosis.
This study showed that genetic variations in the human NRAMP1 gene are associated with susceptibility to smear-positive tuberculosis in Korean patients.
In the homologous human NRAMP1 gene, a total of 11 polymorphisms have been identified, which are being used to test for the linkage of NRAMP1 alleles with human responses to mycobacteria, including susceptibility to tuberculosis and leprosy, as well as BCG immunotherapy in bladder cancer.
These data therefore confirm the importance of SLC11A1 in tuberculosis susceptibility in humans and suggest that SLC11A1 influences tuberculosis susceptibility by regulation of interleukin-10.
These results indicate that variant alleles in the Nramp1 gene are associated with increased mycobacterial replication rather than susceptibility for tuberculosis and may thus confer increased risk of severe disease.
In the present study, we scanned the regulatory and coding region of Nuclear LIM Interactor-Interacting Factor gene (NLI-IF), which is physically close to the tuberculosis-associated gene NRAMP1.
These results indicate that variant alleles in the Nramp1 gene are associated with increased mycobacterial replication rather than susceptibility for tuberculosis and may thus confer increased risk of severe disease.
These findings suggest that the 5'(GT)n polymorphism of NRAMP1 modifies TB susceptibility in this Caucasian population, and could possibly be related to the site of infection among HIV-negative individuals and HIV-coinfected TB.
The 469 + 14 G/C (INT4), 1465 - 85 G/A, and C274T polymorphisms of NRAMP1 and the A/C polymorphism of IL12 3'-UTR were analyzed in ethnic Russians with (N = 58) or without (N = 127) tuberculosis (TB) from Tomsk.
To study the variations in the NRAMP1 gene using five genotypes (274C/T, 577-18G/A, A318V, D543N and 3' untranslated region [UTR]), and the susceptibility of tuberculosis and HIV infection in Taiwanese.
Heterozygosity for the -1082 polymorphism of the IL-10 promoter and heterozygosity for 2 linked polymorphic NRAMP1 variants, D543N and 3' untranslated region, were associated with TB susceptibility and resistance, respectively.