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.
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.
To determine the model of inheritance for genetic susceptibility to tuberculosis, and to test the hypothesis that TNFA and NRAMP1 are candidate susceptibility genes.
The association between SLC11A1 polymorphisms and tuberculosis susceptibility observed in our analyses supports the hypothesis that NRAMP1 might play an important role in the host defense to the development of tuberculosis.
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.
We then examine the putative role of iron-related host genes by focussing on two candidate genes, haptoglobin and NRAMP1, for which there are common polymorphic variants in humans with strong evidence of functionally distinct biochemical phenotypes that would be predicted to influence the course of HIV and TB infections.
Multiple host iron status biomarkers, Haptoglobin and solute carrier family 11, member 1 (SLC11A1) genotypes were modeled to characterize how indicators of host iron metabolism were associated with TB susceptibility.
Many genes involved in tuberculosis susceptibility (e.g., NRAMP1 (SLC11A1), IFNG, NOS2A, VDR, ISG15, TACO, TLR1, TLR, IL18R1, chemokines, PADI, DUSP14, MBL, and MASP-2) have been subjected to epigenetic modification.
To explain the different direction of allelic association between adult and pediatric disease, we hypothesize that NRAMP1 influences the speed of progression from infection to tuberculosis disease.
The natural resistance-associated macrophage protein (NRAMP1), Vitamin-D receptor (VDR) and Tumor necrosis factor (TNF-alpha) have been associated in susceptibility to tuberculosis, but the results have been inconsistent.
The Nramp1 gene influences susceptibility to a variety of intracellular bacteria (including mycobacterial species), but not to Mycobacterium tuberculosis.
Association studies have revealed that host genetic factors, such as human leukocyte antigen and solute carrier family 11 member A1 (NRAMP1), play roles in susceptibility to TB.
The solute carrier family 11 member 1 gene (SLC11A1, formerly known as NRAMP1: natural resistance-associated macrophage protein 1) is one of the host genetic factors reported to affect susceptibility to tuberculosis.
The SLC11A1 gene has been reported to play a role in neutrophil function and is associated with susceptibility to infectious and inflammatory diseases such as tuberculosis or rheumatoid arthritis.
Studies have reported genetic markers to predict TB development in human leukocyte antigen (HLA) and non-HLA genes like killer immunoglobulin-like receptor (KIR), toll-like receptors (TLRs), cytokine/chemokines and their receptors, vitamin D receptor (VDR) and SLC11A1 etc.
Heterozygosity for a newly studied CAAA insertion/deletion polymorphism in the 3'-untranslated region of solute carrier family 11, member 1 (SLC11A1, formerly NRAMP1) was associated with protection against TB in both HIV-positive (OR = 0.70, 95% CI = 0.49-0.99, P = 0.046) and HIV-negative (OR = 0.65, 95% CI = 0.46-0.92, P = 0.014) TB cases, suggesting that the SLC11A1 protein may have a role in innate TB immune responses that influence susceptibility even in immunocompromised individuals.
To explore the potential role of these genes in the susceptibility to pulmonary tuberculosis in a Mexican mestizo population, we evaluated the association of D543N and 3'-UTR polymorphisms in NRAMP1/SLC11 A1 and - 762 and A1513C polymorphisms in P2X(7) genes with the risk for tuberculosis.