We made a minireview on the association of many candidate genes with TB based on recent research studies systematically, such as the human leukocyte antigen (HLA) gene, the solute carrier family 11 member 1 (SLC11A1) gene system, the vitamin D receptor (VDR) gene, the mannan-binding lectin (MBL) gene, the nitric oxide synthase 2A (NOS2A) gene, the speckled 110 (SP110) gene, and the P2X7 receptor (P2X7) gene.
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 address whether Arg1 could perform similar functions in hypoxic regions of TB granulomas, we used a TB murine granuloma model in which NOS2is absent.
PCR-Polyacrylamide Gel Electrophoresis and direct sequencing revealed the association of (CCTTT)10 allele with protection against Tuberculosis in all the three populations (i) independently: Odisha [p = 0.0025, pc = 0.025, OR (95%CI) = 0.5 (0.39-0.82)], Chhattisgarh-tribe [p = 0.0001, pc = 0.001, OR (95%CI) = 0.3 (0.19-0.60)] and Sahariya tribe [p = 0.02, pc = 0.2, OR (95%CI) = 0.27 (0.08-0.84)]; and (ii) together: [p < 0.0001, pc < 0.001, OR (95%CI) = 0.47 (0.35-0.63)].
These results indicate that variants of IFNG+874T/A SNP and NOS2A-954G/C SNP do not influence TB susceptibility or the secretion of nitric oxide radicals in the study population.
Thus, in this mini-review, we summarize the current state of investigation on some of the genetic determinants, such as the candidate polymorphisms of vitamin D, VDBP, Toll-like receptor, nitric oxide synthase 2 and interferon-gamma genes, to generate resistance or susceptibility to M. tuberculosis infection.
We also report the molecular signature of tuberculosis infection, in ATBI patients, the following genes were found to be up-regulated and absent in LTBI individuals: two kinases (JAK3 and p38MAPK), four interleukins (IL-7, IL-2, IL-6, and IFNbeta1), a chemokine (HCC-4) a chemokine receptor (CxCR5), two interleukin receptors (IL-1R2 and IL-18R1), and three additional ones (TRAF5, Smad2, CIITA, and NOS2A).
Multilocus analyses between polymorphisms in SLC11A1 and 11 TB candidate genes detected interactions between SLC11A1 and inducible nitric oxide synthase (NOS2A) in Caucasians (rs3731863 [SLC11A1] x rs8073782 [NOS2A], P = 0.009; rs3731863 [SLC11A1] x rs17722851 [NOS2A], P = 0.007) and toll-like receptor 2 (TLR2) in African-Americans (rs3731865 [SLC11A1] x rs1816702, P = 0.005).
When the NOS2A alleles were stratified into short (8-11) and long (12-16) repeats, significant differences with short repeats were observed between TB patients and all controls (P=0.005, OR=0.63, 95%CI=0.46-0.86).
When the NOS2A alleles were stratified into short (8-11) and long (12-16) repeats, significant differences with short repeats were observed between TB patients and all controls (P=0.005, OR=0.63, 95%CI=0.46-0.86).
Results obtained from studies based on a murine experimental tuberculosis model involving nos2-deficient mice suggest that RNI could regulate M. tuberculosis gene expression in vivo.