Influence of Genetic Polymorphism Towards Pulmonary Tuberculosis Susceptibility

Abstract

Tuberculosis (TB) is still remains the major threat for human health worldwide. Several case-control, candidate-gene, family studies and genome-wide association studies (GWAS) suggested the association of host genetic factors to TB susceptibility or resistance in various ethnic populations. Moreover, these factors modulate the host immune responses to tuberculosis. 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. Highly polymorphic HLA loci may influence antigen presentation specificities by modifying peptide binding motifs. The recent meta-analysis studies revealed the association of several HLA alleles in particular class II HLA-DRB1 with TB susceptibility and valuable marker for disease development especially in Asian populations. Case-control studies have found the association of HLA-DR2 in some populations, but not in other populations, this could be due to an ethnic specific association of gene variants. Recently, GWAS conducted in case-control and family based studies in Russia, Chinese Han, Morocco, Uganda and Tanzania revealed the association of genes such as ASAP1, Alkylglycerol monooxygenase (AGMO), Forkhead BoxP1 (FOXP1), C-terminal domain phosphatase 1 (UBLCP1) and intergenic SNP rs932347C/T with TB. Whereas, SNP rs10956514A/G were not associated with TB in western Chinese Han and Tibetan population. In this review, we summarize the recent findings of genetic variants with susceptibility/resistance to TB.

Diagnostic Usefulness of Cytokine and Chemokine Levels in the Cerebrospinal Fluid of Patients with Suspected Tuberculous Meningitis

“…Clinical studies 12,[50][51][52] have shown that MTB-specific TNF-α response can discriminate latent and active disease state of tuberculosis. It has been reported that dysregulation of TNF-α due to genetic variation 53,54 can increase susceptibility to mycobacterial infection. Tobin et al 53 showed that even TNF-α mediates inflammatory responses to TB, excess production of TNF-α leads to necrosis of macrophage, resulting in extracellular mycobacterial growth that accounts for the worse outcome in TBM.…”

Immune Response to Mycobacterium tuberculosis: A Narrative Review

“…On the other side, the study of TB susceptibility, has shed light onto various components of immunity to mycobacteria in humans. Different genetic polymorphisms which modulate the host immune response in favor of TB infection and disease progression have been identified in human leukocyte antigens (HLA), toll like receptors (TLR), vitamin D receptors (VDR), cytokines with their receptors and many other functional immune components (10, 11). Moreover, mendelian susceptibilities to mycobacterial disease (MSMD) have been identified as clinical conditions with selective susceptibility to poorly virulent mycobacteria in the absence of patent immunodeficiency (12).…”

Interleukin-18 and interferon-γ single nucleotide polymorphisms in Egyptian patients with tuberculosis

“…A relation may occur when the polymorphism itself is functional and leads to altered susceptibility to the disease, or when an allele SNP is in LDS with an allele which is associate with disease susceptibility, or because of a conflicting effect induced by population. Genetic markers in human leukocyte antigen (HLA) and non-HLA genes such as toll-like receptors (TLRs), cytokine/chemokines and their receptors and vitamin D receptor (VDR) have been documented in studies to predict TB susceptibility [ 22 ]. In fact, several studies have shown that genetic variations in cytokines/chemokines genes are associated with susceptibility to as TB as IFN-γ [ 23 ], IL-12 [ 24 ], IL-10 [ 25 ], and others [ 26 ].…”