The Evolutionary History of TLR4 Polymorphisms in Europe

Plantinga, Theo S.; Ioana, Mihai; Alonso, Santos; Izagirre, Neskuts; Hervella, Montserrat; Joosten, Leo A. B.; Meer, J.W.M. van der; Rúa, Concepción de la; Netea, Mihai G.

doi:10.1159/000329492

Cited by 20 publications

(22 citation statements)

References 75 publications

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“…The preponderance of research in sepsis has focused on dissecting roles of the immune cells, innate immune regulation, cytokines, and coagulation factors in response to varying infectious and inflammatory mediators [11, 18]. This meta-analysis mainly focused on the associations between CD14-159C/T polymorphism and susceptibility to sepsis or sepsis-related mortality.…”

Section: Discussionmentioning

confidence: 99%

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Association between the -159C/T polymorphism in the promoter region of the CD14 gene and sepsis: a meta-analysis

Ren

et al. 2017

BMC Anesthesiol

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BackgroundThe association between CD14-159C/T polymorphism and sepsis has been assessed but results of current studies appeared conflicting and inconstant. This analysis was aimed to determine whether the CD14-159C/T polymorphism confers susceptibility to sepsis or is associated with increased risk of death from sepsis.MethodThe authors conducted a comprehensive search of PubMed, EMBASE, ISI Web of Science, Cochrane library, ScienceDirect, Wiley Online Library and CNKI databases according to a prespecified protocol. Language limits were restricted to English and Chinese. Two reviewers independently selected the articles and extracted relevant data onto standardized forms. Disagreements were settled by discussion and suggestions from senior consultants. The strength of association were evaluated by odds ratio (OR) and 95% confidence interval (CI). Studies failed to fit the Hardy-Weinberg-Equilibrium were excluded.ResultsThe research identified a total of 2317 full-text articles of which 14 articles met the predefined inclusion criteria. Meta-analysis was performed for allele frequency of C versus T, as well as genotypes CC + CT versus TT (dominant model), CC versus TT + CT (recessive model), CT versus TT and CC versus TT (additive model). All control samples were in Hardy-Weinberg proportion. No significant association between CD14-159C/T polymorphism and sepsis susceptibility or mortality were detected in the overall population. Nonetheless, subgroup analysis of Asian ethnicity revealed significant association between the CD14-159C/T polymorphism and susceptibility to sepsis in additive model (CC versus TT: OR = 0.52, 95% CI 0.29–0.92, p = 0.03) and recessive model (CC versus CT + TT: OR = 0.50, 95% CI 0.30–0.84, p = 0.009). Of note, three out of the five papers included in the subgroup focused exclusively on burn ICU patients.ConclusionsThis meta-analysis demonstrated that CD14-159C/T polymorphism is likely to be associated with susceptibility to sepsis in Asian population, especially for the TT genotype. However, bias may rise for etiologic reasons because the majority of subjects in the subgroup came from burn ICU. CD14-159C/T polymorphism is not relevant to sepsis mortality in any genetic models, regardless of the ethnicities. Due to the exploratory nature of the study, no adjustment for multiple testing was adopted, and therefore the results should be interpreted with precaution. Well-designed studies with larger sample size and more ethnic groups are required to further validate the results.Electronic supplementary materialThe online version of this article (doi:10.1186/s12871-017-0303-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

“…Several studies tried to establish an association between CD14 polymorphism and sepsis [10, 11]. However, varied conclusions have been obtained in different studies.…”

Section: Introductionmentioning

confidence: 99%

Association between the -159C/T polymorphism in the promoter region of the CD14 gene and sepsis: a meta-analysis

Ren

et al. 2017

BMC Anesthesiol

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“…Our data are in agreement with previous reports showing that mutations and susceptibility alleles for autoimmune diseases such as celiac disease and type 1 diabetes have been maintained in human populations because of past positive selection and adaptation. [30][31][32] Immune response and reproduction are believed to be the main selective pressures that have shaped human evolution. 30,33 Exploring further, the geographic distribution of variants in these two genes will provide a unique model to dissect evolutionary constraints on genes with roles in both immune responses and reproduction.…”

Section: Discussionmentioning

confidence: 99%

Report of four new patients with protein-truncating mutations in C6orf221/KHDC3L and colocalization with NLRP7

et al. 2012

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To date, two maternal-effect genes have been shown to have causative roles in recurrent hydatidiform moles (RHMs); NLRP7 that is mutated in 48-60% of patients with RHMs and C6orf221 (HUGO-approved nomenclature is now KHDC3L), a recently identified gene, that is mutated in 14% of patients with RHMs who are negative for NLRP7 mutations. We sequenced KHDC3L in 97 patients with RHMs and reproductive loss who are mostly negative for NLRP7 mutations. We identified three unrelated patients, each homozygous for one of the two protein-truncating mutations, a novel 4-bp deletion resulting in a frameshift, c.299_302delTCAA, p.Ile100Argfs*2, and a previously described 4-bp deletion, c.322_325delGACT, p.Asp108Ilefs*30, transmitted on a shared haplotype to three patients from different populations. We show that five HM tissues from one of these patients are diploid and biparental similar to HMs from patients with two defective NLRP7 mutations. Using immunofluorescence, we show that KHDC3L protein displays a juxta perinuclear signal and colocalizes with NLRP7 in lymphoblastoid cell lines from normal subjects. Using cell lines from patients, we demonstrate that the KHDC3L mutations do not change the subcellular localization of the protein in hematopoietic cells. Our data highlight the similarities between the two causative genes for RHMs, KHDC3L and NLRP7, in their subcellular localization, the parental contribution to the HM tissues caused by them, and the presence of several founder mutations and variants in both of them indicating positive selection and adaptation.

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“…In addition, the TLR4 polymorphism Asp299Gly has been shown to be associated with otitis-prone condition in human studies 21 and polymorphisms in the TLR4 gene (Asp299Gly and Thr300Gly) are present in 10% of the Caucasian population and have been shown to be associated with numbers health risks, i.e. gram negative sepsis, premature birth 22 . This mouse therefore offers a model in which to characterize the impact of chronic middle ear inflammation on key homeostatic mechanisms in the cochlea and middle ear.…”

Section: Introductionmentioning

confidence: 99%

Inner Ear Tissue Remodeling and Ion Homeostasis Gene Alteration in Murine Chronic Otitis Media

MacArthur¹,

Hausman²,

Kempton³

et al. 2013

Otology &Amp; Neurotology

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Hypothesis Studies were designed to ascertain the impact of chronic middle ear infection on the numerous ion and water channels, transporters and tissue remodeling genes in the inner and middle ear. Background Permanent sensorineural hearing loss is a significant problem resulting from chronic middle ear disease, although the inner ear processes involved are poorly defined. Maintaining a balanced ionic composition of endolymph in the inner ear is crucial for hearing, thus, it was hypothesized this may be at risk with inflammation. Methods Inner and middle ear RNA collected separately from 6 month-old C3H/HeJ mice with prolonged middle ear disease were subjected to qRT-PCR for 8 common inflammatory cytokine genes, 24 genes for channels controlling ion (sodium, potassium, chloride) and water (aquaporin) transport, tight junction claudins, and gap junction connexins, and 32 tissue remodeling genes. Uninfected Balb/c mice were used as controls. Results Significant increase in inner ear inflammatory and ion homeostasis (claudin, aquaporin and gap junction) gene expression, and both up- and down-regulation of tissue remodeling gene expression occurred. Alteration in middle ear ion homeostasis and tissue remodeling gene expression was noted in the setting of uniform upregulation of cytokine genes. Conclusions Chronic inflammatory middle ear disease can impact inner ear ion and water transport functions and induce tissue remodeling. Recognizing these inner ear mechanisms at risk may identify potential therapeutic targets to maintain hearing during prolonged otitis media.

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The Evolutionary History of TLR4 Polymorphisms in Europe

Cited by 20 publications

References 75 publications

Association between the -159C/T polymorphism in the promoter region of the CD14 gene and sepsis: a meta-analysis

Association between the -159C/T polymorphism in the promoter region of the CD14 gene and sepsis: a meta-analysis

Report of four new patients with protein-truncating mutations in C6orf221/KHDC3L and colocalization with NLRP7

Inner Ear Tissue Remodeling and Ion Homeostasis Gene Alteration in Murine Chronic Otitis Media

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