Polymorphisms in the toll-like receptor 9 gene associated with sepsis and multiple organ dysfunction after major blunt trauma

Chen, K.‐H.; Zeng, Lei; Gu, Wei; Zhou, Jian; Du, Ding Yuan; Jiang, Jianxin

doi:10.1002/bjs.7532

Cited by 40 publications

(23 citation statements)

References 18 publications

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“…In addition to the abovementioned effect of rs5743836 on transcription factor binding,14 certain rs352162 alleles have been associated with an increased TNFα production by peripheral blood leucocytes in response to bacterial DNA stimulation 32. Yet, analysis of the exact functional consequences of the AAV-associated TLR9 polymorphisms appears mandatory before any further clues for AAV pathology can be drawn.…”

Section: Discussionmentioning

confidence: 99%

Genetics of toll like receptor 9 in ANCA associated vasculitides

et al. 2013

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Section: Discussionmentioning

confidence: 99%

Genetics of toll like receptor 9 in ANCA associated vasculitides

et al. 2013

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“…Studies have shown TLR9 polymorphisms to be associated with CD and specific TLR9 polymorphisms to be associated with altered TNFα and/or IFNγ levels [14], [15], [16], [17]. In addition, one study has shown interactions between TLR9 polymorphisms and NOD2 variants in patients with CD [18].…”

Section: Resultsmentioning

confidence: 99%

Patients with Inflammatory Bowel Disease Exhibit Dysregulated Responses to Microbial DNA

et al. 2012

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BackgroundA critical role for the gut epithelium lies in its ability to discriminate between pathogens and commensals and respond appropriately. Dysfunctional interactions between microbes and epithelia are believed to have a role in inflammatory bowel disease (IBD). In this study, we analyzed microbiota and gene expression in IBD patients and examined responses of mucosal biopsies to bacterial DNA.MethodsBiopsies were taken from non-inflamed areas of the colon in healthy controls (HC) and Crohn's disease (CD) and ulcerative colitis (UC) patients in remission. Biopsies were snap-frozen or cultured with DNA from Lactobacillus plantarum (LP) or Salmonella dublin (SD). Gene expression was analyzed under basal conditions and in response to DNA. Gene networks were analyzed using Ingenuity Pathways software. Mucosal-associated microbiota was analyzed using terminal restriction fragment length polymorphism. Frequency of single nucleotide polymorphisms in NOD2 and TLR9 was assessed.ResultsPatients with IBD had altered microbiota, enhanced expression of inflammatory genes, and increased correlations between specific gene expression and microbes. Principle component analysis showed CD and UC patients to cluster independently from healthy controls in both gene expression and microbial analysis. DNA from LP stimulated anti-inflammatory pathways in controls and UC patients, but induced an upregulation of IL17A in CD patients. There were no differences in SNP frequencies of TLR9 or NOD2 in the groups.ConclusionsPatients with Crohn's disease exhibit altered responses to bacterial DNA. These findings suggest that the gut response to bacterial DNA may depend not only on the specific type of bacterial DNA, but also on the host.

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“…Cells that express TLR9, which include plasmacytoid dendritic cells (pDCs) and B cells, produce cytokines, chemokines and interferons (27). The TLR9 variant examined in this study has been shown to be associated with chronic inflammatory conditions like Systemic Lupus Erythematosus (SLE), Crohn’s (28) disease and cervical cancer (29) where abnormal sensitization of the immune system by microbial agents plays a role in disease evolution.…”

Section: Discussionmentioning

confidence: 99%

A toll-like receptor 9 (rs352140) variant is associated with placental inflammation in newborn infants

Karody

Reese

Kumar

et al. 2015

The Journal of Maternal-Fetal & Neonatal Medicine

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Objective Chorioamnionitis contributes to premature birth and associated postnatal morbidity. The genetic basis of altered immune responses underlying placental inflammation (PI) remains understudied. The aim of this study was to evaluate the relationship among TLR signaling pathway polymorphisms and different patterns of PI. Methods Prospective cohort study in infants involving cord blood collection and placental examination for PI. 159 infants enrolled in study out of which 28 were term (8 with PI) and 131 preterm (47 with PI). DNA from blood was genotyped for SNPs in TLR2, 4, 5, 9, NFKBI, NFKBIA, TIRAP and IRAK1 genes using multiplexed single base extension assay. Results While there were no differences in BW, GA, gender, race, and SPL among infants with or without PI, there was a higher incidence of PPROM, maternal smoking, drug use and clinical chorioamnionitis among infants with PI. Out of nine TLR variants, only CT and/or TT genotypes of the TLR9 variant (rs352140) were significantly associated (p=0.004) with any PI and maternal pattern of inflammation (p=0.012) both by univariate analysis and logistic regression. Conclusions Presence of a variant T allele in a common SNP (rs352140) in the TLR9 gene whose product recognizes bacterial DNA is associated with increased PI.

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Polymorphisms in the toll-like receptor 9 gene associated with sepsis and multiple organ dysfunction after major blunt trauma

Abstract: TLR9 polymorphisms rs187084 and rs352162 might be used to provide relevant risk estimates for the development of sepsis and MOD in patients with major trauma.

Cited by 40 publications

References 18 publications

Genetics of toll like receptor 9 in ANCA associated vasculitides

Genetics of toll like receptor 9 in ANCA associated vasculitides

Patients with Inflammatory Bowel Disease Exhibit Dysregulated Responses to Microbial DNA

A toll-like receptor 9 (rs352140) variant is associated with placental inflammation in newborn infants

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