Systemic soluble receptor for advanced glycation endproducts is a biomarker of emphysema and associated with AGER genetic variants in patients with chronic obstructive pulmonary disease

Donavan T. Cheng, Deog Kyeom Kim, Debra A. Cockayne, Anton Belousov, Hans Bitter, Michael H. Cho, Annelyse Duvoix, Lisa D. Edwards, David A. Lomas, Bruce E. Miller, Niki Reynaert, Ruth Tal-Singer, Emiel F.M. Wouters, Alvar Agustí, Leonardo M. Fabbri, Alex Rames, Sudha Visvanathan, Stephen I. Rennard, Paul Jones, Harsukh ParmarWilliam MacNee, Gerhard Wolff, Edwin K. Silverman, Ruth J. Mayer, Sreekumar G. Pillai

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

Rationale: Emphysema in chronic obstructive pulmonary disease (COPD) can be characterized by high-resolution chest computed tomography (HRCT); however, the repeated use of HRCT is limited because of concerns regarding radiation exposure and cost. Objectives: To evaluate biomarkers associated with emphysema and COPD-related clinical characteristics, and to assess the relationships of soluble receptor for advanced glycation endproducts (sRAGE), a candidate systemicbiomarker identifiedinthis study, with single-nucleotide polymorphisms (SNPs) in the gene coding for RAGE (AGER locus) and with clinical characteristics. Methods: Circulating levels of 111 biomarkers were analyzed for association with clinical characteristics in 410 patients with COPD enrolled in the TESRA study. sRAGE was also measured in the ECLIPSE cohort in 1,847 patients with COPD, 298 smokers and 204 nonsmokers. The association between 21 SNPs in the AGER locus with sRAGE levels and clinical characteristics was also investigated. Measurements and Main Results: sRAGE was identified as a biomarker of diffusing capacity of carbon monoxide and lung density in the TESRA cohort. In the ECLIPSE cohort, lower sRAGE levels were associated with increased emphysema, increased Global Initiative for Chronic Obstructive Lung Disease stage, and COPD disease status. The associations with emphysema in both cohorts remained significant after covariate adjustment (P < 0.0001). One SNP in the AGER locus, rs2070600, was associated with circulating sRAGE levels both in TESRA (P = 0.0014) and ECLIPSE (7.07 × 10-16), which exceeded genome-wide significance threshold. Another SNP (rs2071288) was also associated with sRAGE levels (P = 0.01) and diffusing capacity of carbonmonoxide (P=0.01) in the TESRA study. Conclusions: Lower circulating sRAGE levels are associated with emphysema severity and genetic polymorphisms in the AGER locus are associated with systemic sRAGE levels.

Original languageEnglish (US)
Pages (from-to)948-957
Number of pages10
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume188
Issue number8
DOIs
StatePublished - Oct 15 2013

Keywords

  • DL
  • Lung density
  • Single-nucleotide polymorphism

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Fingerprint Dive into the research topics of 'Systemic soluble receptor for advanced glycation endproducts is a biomarker of emphysema and associated with AGER genetic variants in patients with chronic obstructive pulmonary disease'. Together they form a unique fingerprint.

  • Cite this

    Cheng, D. T., Kim, D. K., Cockayne, D. A., Belousov, A., Bitter, H., Cho, M. H., Duvoix, A., Edwards, L. D., Lomas, D. A., Miller, B. E., Reynaert, N., Tal-Singer, R., Wouters, E. F. M., Agustí, A., Fabbri, L. M., Rames, A., Visvanathan, S., Rennard, S. I., Jones, P., ... Pillai, S. G. (2013). Systemic soluble receptor for advanced glycation endproducts is a biomarker of emphysema and associated with AGER genetic variants in patients with chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, 188(8), 948-957. https://doi.org/10.1164/rccm.201302-0247OC