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.
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.
On the basis of linkage disequilibrium pattern, three genetic markers from SLC11A1 and one from the nearby IL8RB locus were selected and examined for association with TB susceptibility.
Polymorphisms at the four loci had no statistically significant association between the SLC11A1 variants and susceptibility to TB in subjects of European descent, while they showed a statistically significant association in Asian subjects (except the INT4 variant), African subjects (except the 3'UTR variant) and the population as a whole (except the INT4 variant).
Polymorphisms in the NRAMP1 gene, VDR gene, HLA-DRB1 gene, and HLA-DQB1 gene are statistically associated with susceptibility to TB in the Chinese Kazakh population.
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 important candidate genes like human leucocyte antigen/alleles and non-human leucocyte antigen genes, such as cytokines and their receptors, chemokines and their receptors, pattern recognition receptors (including toll-like receptors, mannose binding lectin and the dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin), solute carrier family 11A member 1 (formerly known as natural resistance-associated macrophage protein 1) and purinergic P2X7 receptor gene polymorphisms, have been associated with differential susceptibility to TB in various ethnic populations.
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.
Similarly, no significant differences were observed between NRAMP1 polymorphisms and rheumatoid factor positivity and erosive disease in RA and localization of TB.
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.
Susceptibility to TB-IRD associated with carriage of TNFA-1031*T (rs1799964; P=0.05) and SLC11A1 D543N*G (rs17235409; P=0.04) in Cambodian patients and carriage of IL18-607*G (rs1946518; P=0.02) and VDR FokI (F/f)*T (rs10735810; P=0.05) in Indian patients.
The (GT)n promoter alleles 2 and 3 (rs534448891), which alter SLC11A1 expression, were significantly associated with tuberculosis (OR=1.47 (1.30-1.66), OR=0.76 (0.65-0.89), respectively) and infectious disease (OR=1.25 (1.10-1.42), OR=0.83 (0.74-0.93), respectively).
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.
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.
The Nramp1 gene influences susceptibility to a variety of intracellular bacteria (including mycobacterial species), but not to Mycobacterium tuberculosis.
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 natural resistance-associated macrophage protein 1 (NRAMP1) gene is associated with susceptibility to Mycobacterium tuberculosis in humans and to bacillus Calmette-Guérin (BCG) in mice.
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.
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.
The distribution of three polymorphisms in the natural resistance-associated macrophage protein gene (NRAMP1) including INT4, D543N and 3'UTR was examined for a possible association with susceptibility to TB.