Association of RAGE gene multiple variants with the risk for COPD and asthma in northern Han Chinese

Abstract

Clinical and experimental data have shown that the receptor for advanced glycation end products (RAGE) is implicated in the pathogenesis of respiratory disorders. In this study, we genotyped five widely-evaluated variants in RAGE gene, aiming to assess their association with the risk for chronic obstructive pulmonary disease (COPD) and asthma in northern Han Chinese. Genotypes were determined in 105 COPD patients, 242 asthma patients and 527 controls. In single-locus analysis, there was significant difference in the genotype distributions of rs1800624 between COPD patients and controls ( p =0.022), and the genotype and allele distributions of rs1800625 differed significantly ( p =0.040 and 0.016) between asthma patients and controls. Haplotype analysis revealed that haplotype T-A-G-T (allele order: rs1800625, rs1800624, rs2070600, rs184003) was significantly associated with a reduced COPD risk (OR=0.32, 95% CI: 0.06-0.60), and haplotype T-A-A-G was significantly associated with a reduced asthma risk (OR=0.19, 95% CI: 0.04-0.96). Further haplotype-phenotype analysis showed that high- and low-density lipoprotein cholesterol and blood urea nitrogen were significant mediators for COPD ( p sim =0.041, 0.043 and 0.030, respectively), and total cholesterol was a significant mediator for asthma ( p sim =0.009). Taken together, our findings indicate that RAGE gene is a promising candidate for COPD and asthma, and importantly both disorders are genetically heterogeneous.

Chitinase 3‐like 1 polymorphisms and risk of chronic obstructive pulmonary disease and asthma in a Chinese population

“…Healthy controls were enrolled for the study in accordance with previously reported criteria 13 : (i) they had not been diagnosed with COPD, asthma or any other respiratory disease and (ii) they had no history of respiratory allergic diseases or any other respiratory symptom. Spirometry without bronchodilation was performed for the controls.…”

“…Individuals were excluded from the study in accordance with previously reported criteria 13 : (i) they had been diagnosed with cancer within the last 5 years,; (ii) they had experienced venous thromboembolism; (iii) they had been immobilized for > 3 days; (iv) they had a suspected acute inflammatory or infectious disease; (v) they had received anticoagulant therapy; (vi) they had smoked with an abstinence of only < 6 months; (vii) they were diagnosed with diabetes mellitus, heart failure, chronic renal failure or liver disease at the time; (viii) they were pregnant or under hormone‐replacement therapy; or (ix) they had a history of stroke or acute coronary syndrome.…”

“…Protocols for genomic DNA extraction and PCR procedures were reported previously 13 . Briefly, DNA was extracted from peripheral whole blood using the King Fisher Flex purification system (Thermo Scientific, Waltham, MA, USA) on a robotic pipetting workstation (Tecan, Morrisville, NC, USA).…”

The axis of the receptor for advanced glycation endproducts in asthma and allergic airway disease

“…However, the association of rs2070600 with asthma risk remains unclear and requires more extensive investigation to clarify any association. 72,73 Although RAGE is most abundantly expressed in type 1 alveolar epithelial cells (AEC) 8 it is also expressed in a number of structural and immune cells involved in asthma pathogenesis. This includes, airway epithelia, 74 airway smooth muscle cells (ASMC), 75 lung endothelia, 76 lung fibroblasts, 77 alveolar macrophages, 78 eosinophils, 79 neutrophils, 80 mast cells, 81 lymphocytes 82 and ILC2s.…”

“…An increase in RAGE‐signaling likely contributes to augmented inflammation, which could exacerbate airway obstruction and disease severity. However, the association of rs2070600 with asthma risk remains unclear and requires more extensive investigation to clarify any association 72,73 . Although RAGE is most abundantly expressed in type 1 alveolar epithelial cells (AEC) 8 it is also expressed in a number of structural and immune cells involved in asthma pathogenesis.…”