Toll-like receptor heterodimer variants protect from childhood asthma

Kormann, Michael; Depner, Martin; Hartl, Dominik; Klopp, Norman; Illig, Thomas; Adamski, Jerzy; Vogelberg, Christian; Weiland, Stephan K.; Mutius, Erika von; Kabesch, Michael

doi:10.1016/j.jaci.2008.04.039

Cited by 135 publications

(159 citation statements)

References 27 publications

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“…23 Although several candidate gene studies did find TLR6 polymorphisms to be associated with atopy, 5,8,24 this has to date not yet been confirmed in genome-wide association studies. However, Figure 1.…”

Section: Discussionmentioning

confidence: 96%

“…21 These data suggest that the TLR6 gene controls Th1 differentiation, whereas the absence of TLR6-mediated signals generates Th2 responses. Moreover, Kormann et al 5 showed another SNP located in the TLR6 gene, that is, rs5743789, to be associated with increased mRNA expression. Carriers of the minor allele of this SNP showed increased Th1 cytokine expression, and reduced Th2 cytokine production after stimulation with its ligand.…”

Section: Discussionmentioning

confidence: 99%

“…Variations in genes encoding TLRs and CD14 are suggested to alter the capability to recognize microbes or alter the amount of gene product, leading to inadequate immune responses and increasing the susceptibility for atopic disease. 5,9 In the case of childhood ALL, much less is known about the role of genes involved in innate immunity. 10 Examining the genetic basis of the inverse association between childhood ALL and atopic disease might help towards elucidating the etiology of childhood ALL.…”

Section: Introductionmentioning

confidence: 99%

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Polymorphisms in the TLR6 gene associated with the inverse association between childhood acute lymphoblastic leukemia and atopic disease

et al. 2011

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Polymorphisms in the TLR6 gene associated with the inverse association between childhood acute lymphoblastic leukemia and atopic disease

et al. 2011

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“…The common genetic risks for bronchiolitis and asthma have recently been reviewed (Bartlett et al, 2009). These genes include those involved in the innate/Th1 response to infection [e.g., Toll-like receptors and CD14 (Hong et al, 2007;Kormann et al, 2008;Bjornvold et al, 2009)], and those encoding for interferons [e.g., interferon-γ gene (Kumar and Ghosh, 2008), interferon regulatory factor-1 gene (Schedel et al, 2008)], as well as the interleukin-13 and interleukin-14 genes (Forton et al, 2009). The sequence variant rs7216389 in ORMDL3 was shown to be associated with the risk of childhood asthma in a genome-wide association study of asthma (Moffatt et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

ORMDL3 variants associated with bronchiolitis susceptibility in a Chinese population

Xt¹,

Liu²,

Ll³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Recent studies revealed common genetic risks for both viral bronchiolitis and asthma. Genome-wide association studies revealed that rs7216389 in the ORMDL3 gene is associated with childhood asthma. We conducted a case-control study examining the associations between ORMDL3 polymorphisms (rs7216389, rs12603332, and rs11650680) and bronchiolitis susceptibility/viral findings among 247 infant bronchiolitis cases and 190 healthy controls. We genotyped single nucleotide polymorphisms by matrix-assisted laser desorption/ ionization-time-of-flight mass spectrometry and detected respiratory viruses with multiplex reverse transcriptase-polymerase chain reaction. Only the genotype and allele frequencies of rs7216389 significantly differed between bronchiolitis and controls. The frequencies of the TT homozygote and the T allele of rs7216389 were significantly higher in the bronchiolitis patients (P = 0.0325; P = 0.0089, respectively). Polymorphisms were not associated with bronchiolitis severity. Cases were further stratified by viral infection, but no significant differences 19155-19162 (2015) in the ORMDL3 genotype between the virus-detected group (e.g., respiratory syncytial virus alone, respiratory virus alone, virus detected) and no-virus-detected group were observed. Bronchiolitis is associated with the ORMDL3 gene in Chinese children, and there were no significant associations between genetic variations and disease severity or respiratory viruses. The TT homozygote and the T allele of rs7216389 in ORMDL3 increased bronchiolitis risk. The rs7216389 polymorphism may be a predictor for identifying infants with predisposition to virusinduced wheezing to persistent asthma.

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“…Kormann and colleagues reported associations between TLR polymorphisms in TLRs 1, 2, and 6 and asthma development in children living in urban locations. 112 Several birth cohort studies from the Netherlands report a significant association between TLR polymorphisms that may result from TLR2 participation in Treg-cell signaling. Treg signaling is important in balancing immune responses to maintain or acquire tolerance against allergies.…”

Section: Tlr and Interindividual Variability In Disease Susceptibilitymentioning

confidence: 99%

Impact of air pollution on lung inflammation and the role of Toll-like receptors

Plummer¹,

Smiley‐Jewell²,

Pinkerton³

2012

IJICMR

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Abstract:The link between air pollution and adverse pulmonary health effects is well established. The National Ambient Air Quality Standards were formulated to protect human health. These standards are strictly enforced based on strong associations between elevated air pollution levels and increased emergency room visits and hospitalizations due to respiratory conditions. Impacts of air pollution on lung health occur due to the direct interaction between the external environment and internal biological systems and processes. The innate immune system is one of the first lines of defense against inhaled air contaminants and is characterized by activation of key signaling pathways and inflammatory cell recruitment to the lung. Numerous independent and often redundant pathways participate in innate and adaptive immune responses. Given the impact of air pollution on human health, extensive research efforts have aimed to characterize the mechanisms of response to various air pollutants and evaluate risk factors contributing to individual susceptibility. A significant body of evidence exists to document air pollution-induced alterations in proinflammatory or oxidative signaling molecules. However, the role of specific pathways participating in the propagation of the inflammatory effects remains unclear. One hypothesis for interindividual susceptibility to inhaled air pollutants is that genetic polymorphisms in inflammatory or oxidative stress pathways may contribute to the diverse range of the inflammatory response. Activation of numerous receptors associated with airway cells culminates in the translocation of nuclear factor-kappa B and other transcription factors to the nucleus, and therefore initiation of altered signaling of proinflammatory mediators. Alterations in the transcription and expression of inflammatory mediators following exposure to air pollution are well documented. However, the interaction between specific air pollutants and specific cell surface and intracellular receptors has not been clearly defined. Involvement of specific pathways in the innate immune response may be dependent on differential physical and chemical characteristics of air pollution. One pathway implicated in the response to inhaled air pollutants is initiated by the activation of Toll-like receptors (TLRs). TLRs and downstream proinflammatory mediators are well studied for their role in pathogen response, yet gaps in the understanding of TLR response to nonpathogenic agents, such as air pollution, exist. TLRs are associated with inflammation and allergy, and emerging evidence suggests they may also play a role in the response and susceptibility to air pollution. However, the specific component, exogenous or endogenous, responsible for the association between air pollution and TLR activation has yet to be clearly identified. Improved understanding of pulmonary response mechanisms and potential mediators of susceptibility to air pollution, including the role of TLRs, may contribute to a reduction of the health burden of air pollutio...

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Toll-like receptor heterodimer variants protect from childhood asthma

Cited by 135 publications

References 27 publications

Polymorphisms in the TLR6 gene associated with the inverse association between childhood acute lymphoblastic leukemia and atopic disease

Polymorphisms in the TLR6 gene associated with the inverse association between childhood acute lymphoblastic leukemia and atopic disease

ORMDL3 variants associated with bronchiolitis susceptibility in a Chinese population

Impact of air pollution on lung inflammation and the role of Toll-like receptors

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