Does RAGE protect smokers from COPD?

Young, Robert P.; Hay, Bryan A.

doi:10.1183/09031936.00041711

Cited by 14 publications

(13 citation statements)

References 11 publications

(8 reference statements)

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“…The S allele of this SNP results in glycine being changed to serine at position 82 of the third exon encoding the RAGE protein (a nonsynonymous change altering the polarity of the amino acid at this position) and has been shown to be associated with both reduced serum levels of sRAGE and increased sRAGE signaling compared with the more common G allele (Smith et al, 2011). This change in sRAGE signaling affects downstream gene expression through mitogen-activated protein kinases and NF-kB, both of which have been implicated in the inflammatory responses in COPD (Young et al, 2011a).…”

Section: Discussionmentioning

confidence: 96%

Association of Polymorphisms of the Receptor for Advanced Glycation End Products Gene with COPD in the Chinese Population

Cheng²,

Ma³

et al. 2014

DNA and Cell Biology

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The receptor for advanced glycation end products (RAGE) is a cell surface molecule of the immunoglobulin superfamily that binds diverse endogenous ligands involved in the development of chronic diseases and inflammatory damage. A growing body of evidence has suggested that RAGE is involved in the development and progression of chronic obstructive pulmonary disease (COPD). The present study investigated the existence of an association among three polymorphisms (-374T/A, -429T/C, and G82S) of the RAGE gene with the risk of COPD in the Chinese population. The RAGE genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism in 216 patients with COPD and 239 age-matched healthy individuals. Our study demonstrated that the frequencies of the GS genotype and the S allele in the G82S mutation were significantly higher in COPD patients than in controls (odds ratios [OR]=1.70, 95% confidence interval [CI]: 1.15-2.50, p=0.0098 and OR=1.42, 95% CI: 1.06-1.91, p=0.023, respectively). Further stratification analysis by smoking status revealed that the presence of the GS genotype conferred a higher risk of developing COPD in current smokers (p=0.044). In contrast, mutations at -374T/A and -429T/C did not demonstrate any association with COPD, even after taking into account the patients' smoking history. Our study provides preliminary evidence that the G82S polymorphism in the RAGE gene is associated with an increased risk of COPD and that the GS genotype of the G82S variant is a risk factor for COPD in the Chinese population.

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Section: Discussionmentioning

confidence: 96%

Association of Polymorphisms of the Receptor for Advanced Glycation End Products Gene with COPD in the Chinese Population

Cheng²,

Ma³

et al. 2014

DNA and Cell Biology

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“…The G82S polymorphism of RAGE results in glycine being changed to serine at position 82 of the third exon encoding the RAGE protein and has been shown to be associated with both reduced serum levels of sRAGE and increased sRAGE signaling compared with the more common G allele [19, 29, 30]. This change in sRAGE signaling affects downstream gene expression through MAPK and NF- κ B, both of which have been implicated in the inflammatory response in AAA [31]. In the present study, we showed that the serum levels of sRAGE were significantly decreased in AAA patients compared to the controls, supporting the potential role for the RAGE axis in the pathology of AAA.…”

Section: Discussionmentioning

confidence: 99%

Association of Polymorphisms of the Receptor for Advanced Glycation End Products Gene and Susceptibility to Sporadic Abdominal Aortic Aneurysm

Yao

Zhuang

You

et al. 2015

BioMed Research International

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Accumulating evidence has suggested that receptor for advanced glycation end products (RAGE) is involved in the development and progression of human abdominal aortic aneurysms (AAAs). However, the association between RAGE gene polymorphisms and AAA has not yet been determined. The present study was aimed at analyzing the potential association between the RAGE gene polymorphisms and AAAs. A cohort of 381 patients and 436 age-matched healthy controls were genotyped to detect the three RAGE polymorphisms (−374 T/A, −429 T/C, and G82S) using SNaPshot. Our study demonstrated a significant difference in the genotype and allele frequencies of the RAGE G82S polymorphism between the AAA patients and the controls. Further stratification by gender and smoking status revealed that the presence of the RAGE 82S allele confers a higher risk for developing AAA in men and smokers. Moreover, AAA patients with the variant 82S allele of RAGE presented with reduced serum soluble RAGE (sRAGE) production, and this decrease was more significant in men and smokers with AAA. Our study provides preliminary evidence that the 82S allele of RAGE is a risk factor for AAA. This new piece of knowledge regarding RAGE may be clinically important for the prevention and therapy of AAAs.

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“…However, one of the variants most frequently associated with pulmonary phenotypes is rs2070600, a relatively uncommon increased FEV 1 /FVC in their general population samples (36,37). The minor allele of the rs2070600 variant was also associated with protection with respect to COPD in a relatively small population of smokers (38).…”

Section: Genetics Of Ager In Pulmonary Function Copd and Emphysemamentioning

confidence: 99%

Circulating Soluble Receptor for Advanced Glycation End Products (sRAGE) as a Biomarker of Emphysema and the RAGE Axis in the Lung

Yonchuk

Silverman

Bowler

et al. 2015

Am J Respir Crit Care Med

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Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease that has been traditionally characterized by incompletely reversible airflow limitation. Yet, the latter is poorly correlated with many other clinically relevant characteristics of the disease. Thus, the identification of biomarkers to more accurately assess this heterogeneity and disease severity may facilitate the discovery and development of new treatments and better management of patients with COPD. One molecule that has attracted attention as a potentially useful biomarker specifically for the emphysema subpopulation is the soluble receptor for advanced glycation end products (sRAGE). As the soluble isoform of a key proinflammatory signaling receptor, sRAGE acts as a "decoy" for RAGE ligands and prevents their interaction with the receptor. Multiple reports have now linked sRAGE to COPD, and more specifically to emphysema, and evidence is accumulating that this link is likely mechanistic in nature. Here we review the current state of knowledge about sRAGE biology, the mechanistic links to COPD, and the evidence for using it as a biomarker for emphysema. We also discuss sRAGE as a potential target for therapeutic intervention in COPD.

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Does RAGE protect smokers from COPD?

Cited by 14 publications

References 11 publications

Association of Polymorphisms of the Receptor for Advanced Glycation End Products Gene with COPD in the Chinese Population

Association of Polymorphisms of the Receptor for Advanced Glycation End Products Gene with COPD in the Chinese Population

Association of Polymorphisms of the Receptor for Advanced Glycation End Products Gene and Susceptibility to Sporadic Abdominal Aortic Aneurysm

Circulating Soluble Receptor for Advanced Glycation End Products (sRAGE) as a Biomarker of Emphysema and the RAGE Axis in the Lung

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