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

• Published in: American journal of respiratory and critical care medicine Vol. 188; no. 8; pp. 948 - 957
• Main Authors: CHENG, Donavan T, DEOG KYEOM KIM, REYNAERT, Niki, TAL-SINGER, Ruth, WOUTERS, Emiel F. M, AGUSTI, Alvar, FABBRI, Leonardo M, RAMES, Alex, VISVANATHAN, Sudha, RENNARD, Stephen I, JONES, Paul, PARMAR, Harsukh, COCKAYNE, Debra A, MACNEE, William, WOLFF, Gerhard, SILVERMAN, Edwin K, MAYER, Ruth J, PILLAI, Sreekumar G, BELOUSOV, Anton, BITTER, Hans, CHO, Michael H, DUVOIX, Annelyse, EDWARDS, Lisa D, LOMAS, David A, MILLER, Bruce E
• Format: Journal Article
• Language: English
• Published: New York, NY American Thoracic Society 15.10.2013
• Subjects: Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Biomarkers - blood; Chronic obstructive pulmonary disease, asthma; Emphysema - blood; Emphysema - diagnostic imaging; Emphysema - genetics; Female; Humans; Intensive care medicine; Lung - diagnostic imaging; Male; Medical sciences; Middle Aged; Pneumology; Polymorphism, Single Nucleotide - genetics; Pulmonary Disease, Chronic Obstructive - blood; Pulmonary Disease, Chronic Obstructive - genetics; Receptor for Advanced Glycation End Products; Receptors, Immunologic - blood; Receptors, Immunologic - genetics; Severity of Illness Index; Tomography, Spiral Computed; Intensive care; Lung; Biological marker; DL; Systemic; lung density; Soluble form; Density; Glycation; Association; Bronchus disease; Advanced stage; Chronic obstructive pulmonary disease; Obstructive pulmonary disease; Disseminated; single-nucleotide polymorphism; Resuscitation; Biological receptor; Human; Lung disease; Respiratory disease; Genetic variant; Patient; Single nucleotide polymorphism; Emphysema
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.201302-0247OC

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. 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 systemic biomarker identified in this study, with single-nucleotide polymorphisms (SNPs) in the gene coding for RAGE (AGER locus) and with clinical characteristics. 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. 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 carbon monoxide (P = 0.01) in the TESRA study. Lower circulating sRAGE levels are associated with emphysema severity and genetic polymorphisms in the AGER locus are associated with systemic sRAGE levels. Clinical trial registered with www.clinicaltrials.gov (NCT 00413205 and NCT 00292552).