A Functional Haplotype in the 3′Untranslated Region of<i>TNFRSF1B</i>Is Associated with Tuberculosis in Two African Populations

Möller, Marlo; Flachsbart, Friederike; Till, Andreas; Thye, Thorsten; Horstmann, Rolf D.; Meyer, Christian G.; Osei, Ivy; Helden, Paul D. van; Hoal, Eileen G.; Schreiber, Stefan; Nebel, Almut; Franke, André

doi:10.1164/rccm.200905-0678oc

Cited by 25 publications

(12 citation statements)

References 41 publications

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“…An association between TB and TNFR1 was reported in a Ugandan population (216). A single TNFR1 SNP (rs3397) and a 3=-UTR haplotype (GTT) were associated with TB resistance in Ghana and South Africa (147). Possible evolutionary selection pressure appears to affect TNF gene expression rather than protein structure (1, 259), a common finding among the TB susceptibility genes, as regulation of gene expression may be a prevalent selection mechanism in evolution.…”

Section: Cytokines and Chemokinesmentioning

confidence: 99%

Innate Immune Gene Polymorphisms in Tuberculosis

2012

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ABSTRACTTuberculosis (TB) is a leading cause worldwide of human mortality attributable to a single infectious agent. Recent studies targeting candidate genes and “case-control” association have revealed numerous polymorphisms implicated in host susceptibility to TB. Here, we review current progress in the understanding of causative polymorphisms in host innate immune genes associated with TB pathogenesis. We discuss genes encoding several types of proteins: macrophage receptors, such as the mannose receptor (MR, CD206), dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN, CD209), Dectin-1, Toll-like receptors (TLRs), complement receptor 3 (CR3, CD11b/CD18), nucleotide oligomerization domain 1 (NOD1) and NOD2, CD14, P2X7, and the vitamin D nuclear receptor (VDR); soluble C-type lectins, such as surfactant protein-A (SP-A), SP-D, and mannose-binding lectin (MBL); phagocyte cytokines, such as tumor necrosis factor (TNF), interleukin-1β (IL-1β), IL-6, IL-10, IL-12, and IL-18; chemokines, such as IL-8, monocyte chemoattractant protein 1 (MCP-1), RANTES, and CXCL10; and other important innate immune molecules, such as inducible nitric oxide synthase (iNOS) and solute carrier protein 11A1 (SLC11A1). Polymorphisms in these genes have been variably associated with susceptibility to TB among different populations. This apparent variability is probably accounted for by evolutionary selection pressure as a result of long-term host-pathogen interactions in certain regions or populations and, in part, by lack of proper study design and limited knowledge of molecular and functional effects of the implicated genetic variants. Finally, we discuss genomic technologies that hold promise for resolving questions regarding the evolutionary paths of the human genome, functional effects of polymorphisms, and corollary impacts of adaptation on human health, ultimately leading to novel approaches to controlling TB.

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Section: Cytokines and Chemokinesmentioning

confidence: 99%

Innate Immune Gene Polymorphisms in Tuberculosis

2012

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“…More recently, zebrafish and nonhuman primate models have shown that although TNF is important for overcoming acute infection and preventing reactivation, granuloma formation overall is normal in the absence of TNF (61, 62). In humans, genetic heterogeneity of the TNFR has been associated with increased susceptibility to active TB in Africa (63). The increased incidence of TB among patients treated with anti-TNF agents for inflammatory diseases underscores the importance of TNF (64).…”

Section: Adaptive Immune Responses In Establishing and Maintaining Lamentioning

confidence: 99%

Understanding Latent Tuberculosis: A Moving Target

Lin

Flynn

2010

The Journal of Immunology

399

303

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Tuberculosis (TB) remains a threat to the health of people worldwide. Infection with Mycobacterium tuberculosis can result in active TB or, more commonly, latent infection. Latently infected persons, of which there are estimated to be ~2 billion in the world, represent an enormous reservoir of potential reactivation TB, which can spread to other people. The immunology of TB is complex and multifaceted. Identifying the immune mechanisms that lead to control of initial infection and prevent reactivation of latent infection is crucial to combating this disease.

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“…9,10 TNFRSF1B polymorphism has been investigated in diseases such as tuberculosis, osteoporosis and hypertension. [13][14][15] In this study, we found that the 15 bp insertion allele near the promoter region of TNFRSF1B was associated with an increased risk for migraine when data from individuals with the insertion was compared to data from the group with the 15 bp deletion allele. Our data suggested that the polymorphism near the promoter region of TNFRSF1B may be associated with the occurrence of migraine.…”

Section: Discussionmentioning

confidence: 70%