CD14 and toll-like receptor 4: a link between infection and acute coronary events?

Arroyo-Espliguero, Ramón; Avanzas, Pablo; Jeffery, Steve; Kaski, JC

doi:10.1136/hrt.2002.001297

Cited by 102 publications

(96 citation statements)

References 74 publications

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“…9 In addition, several candidate gene studies have been conducted, testing variants in genes involved in inflammation, for example, CD14, TLR4 and VCAM1, for association with atherosclerosis and significant associations have been reported by some groups. 10,11 Notably, the majority of these studies were conducted in European populations and the results could not be replicated in Chinese Han populations. This suggests that there are substantial differences in the genetic contributors to CAD between these populations.…”

Section: Introductionmentioning

confidence: 99%

Common polymorphisms in ITGA2, PON1 and THBS2 are associated with coronary atherosclerosis in a candidate gene association study of the Chinese Han population

Wang

Xie

et al. 2010

J Hum Genet

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Coronary atherosclerosis is a complex and progressive condition that involves many biological pathways, including the oxidative stress and inflammatory response pathways. To investigate the association between common genetic variation within these two pathways and coronary atherosclerosis, we performed a comprehensive two-stage candidate gene association study in a Chinese Han population. In stage I, 936 tag single-nucleotide polymorphisms (SNPs) within 116 candidate genes were genotyped in 293 coronary atherosclerosis cases and 293 age-and gender-matched healthy controls. In stage II, 51 SNPs from stage I were selected and further genotyped in an additional 1030 cases and 764 controls. In allele-and genotype-based association tests of stage II and a meta-analysis across the two stages, we identified three SNPs within three genes significantly associated with the disease, namely rs3212556 in ITGA2 (P CMH ¼9.20Â10 À5 ), rs854563 in PON1 (P CMH ¼1.92Â10 À4 ) and rs9283851 in THBS2 (P CMH ¼3.00Â10 À3 ). Haplotype analysis provided further supporting evidence for the association of rs3212556 (P global o10 À4 ) and rs854563 (P global o10 À4 ). Our study has identified three SNPs within ITGA2, PON1 and THBS2 that are associated with coronary atherosclerosis.

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Section: Introductionmentioning

confidence: 99%

Common polymorphisms in ITGA2, PON1 and THBS2 are associated with coronary atherosclerosis in a candidate gene association study of the Chinese Han population

Wang

Xie

et al. 2010

J Hum Genet

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“…3 For instance, Toll-like receptor 4 (TLR4) and CD14 are components of a plasma membrane receptor complex mediating phagocyte activation by bacterial lipopolysaccharide 4 and endogenous ligands such as heat shock proteins, fibronectin and hyaluronate fragments. 5 Polymorphic diversity in the receptor complex components may modulate the magnitude of inflammatory response.…”

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confidence: 99%

Polymorphism at position +896 of the toll-like receptor 4 gene interferes with rapid response to treatment in rheumatoid arthritis

Kuuliala

Orpana

Leirisalo‐Repo

et al. 2006

Annals of the Rheumatic Diseases

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The aim of this study was to determine whether the +896 ARG substitution of the Toll-like receptor 4 (TLR4) gene, causing the Asp299RGly change in the extracellular domain of TLR4, influences treatment response in recent-onset rheumatoid arthritis. 169 patients with rheumatoid arthritis were genotyped from the Finnish Rheumatoid Arthritis Combination Therapy trial, in which they were treated either with only one disease-modifying antirheumatic drug (DMARD) with or without prednisolone (single group), or with three DMARDs and prednisolone (combination group). Patients homozygotic for the wild-type +896A allele were compared with those having the polymorphic G allele in terms of early clinical response (at 6 months) by the 28-joint Disease Activity Score (DAS28). 1 of 20 (5%; (95% (confidence interval (CI) 1 to 5)) patients of the single group with TLR4 +896AG or GG and 29 of 67 (43%; (95% CI 31 to 56)) patients with AA were in remission (p = 0.001). DAS28 of the single group with TLR4 +896AG or GG was higher than with AA (p = 0.019). In the combination group, remission rates and DAS28 values were comparable between the genotypes. The polymorphic TLR4 +896G allele may impair treatment response to single DMARD treatment in recent-onset rheumatoid arthritis.

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“…TLRs are transmembrane receptors that normally bind to microbial components such as lipopolysaccharide (LPS) and subsequently activate a signaling pathways that lead to production of cytokines, some of which can induce an acute phase response (Michelsen et al 2004). In particular, TLR4, which recognizes LPS, is closely associated with cardiovascular disease (Arroyo-Espliguero et al 2004;Michelsen et al 2004). Therefore, it was of interest to determine the role, if any, for TLR4 (and hence for LPS) in any increases in acute phase proteins that may be associated with ethanol consumption.…”

Section: Introductionmentioning

confidence: 99%

An explanation for the paradoxical induction and suppression of an acute phase response by ethanol

Pruett

2006

Alcohol

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Binge ethanol (EtOH) consumption suppresses inflammatory responses and resistance to infection, but paradoxically it is associated with increased levels of acute phase proteins (which are indicators of inflammation) and an increased risk of inflammation mediated pathologies such as cardiovascular disease and cirrhosis of the liver. The latter effect may be mediated by increased translocation of bacteria leading to activation of toll-like receptor 4 (TLR4). In this study, the dose-response and time course of the effects of EtOH alone or EtOH in conjunction with a TLR 4 agonist (LPS) were evaluated in mice. Ethanol alone at a dosage of 6 g/kg induced an acute phase response (as indicated by ELISA for serum amyloid A and serum amyloid P) that was maximal 24 hr after dosing. Lower dosages of EtOH did not have this effect but did suppressed the acute phase response to LPS and the production of IL-6 up to 3 hr after dosing. EtOH at 6 g/kg did not induce an acute phase response in C3H/HeJ (TLR4 mutant) mice, indicating that this response is mediated through TLR4. These results provide a resolution for the apparently paradoxical pro-and anti-inflammatory actions of EtOH with regard to acute phase responses.

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CD14 and toll-like receptor 4: a link between infection and acute coronary events?

Cited by 102 publications

References 74 publications

Common polymorphisms in ITGA2, PON1 and THBS2 are associated with coronary atherosclerosis in a candidate gene association study of the Chinese Han population

Common polymorphisms in ITGA2, PON1 and THBS2 are associated with coronary atherosclerosis in a candidate gene association study of the Chinese Han population

Polymorphism at position +896 of the toll-like receptor 4 gene interferes with rapid response to treatment in rheumatoid arthritis

An explanation for the paradoxical induction and suppression of an acute phase response by ethanol

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