Research Paper Volume 11, Issue 10 pp 3220—3237

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

Hongtao Niu 1, 2, 4, 5, , Wenquan Niu 3, 4, 5, , Tao Yu 2, 3, 4, 5, , Feng Dong 3, 4, 5, , Ke Huang 2, 4, 5, , Ruirui Duan 1, 2, 4, 5, , Shiwei Qumu 2, 4, 5, , Minya Lu 1, 2, 4, 5, , Yong Li 4, 5, 6, , Ting Yang 1, 2, 3, 4, 5, 6, , Chen Wang 1, 2, 4, 5, ,

  • 1 Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
  • 2 Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing 100029, China
  • 3 Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China
  • 4 National Clinical Research Center for Respiratory Diseases, Beijing 100029, China
  • 5 Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing 100029, China
  • 6 Clinical Diagnosis Department of Respiratory Diseases Center, China-Japan Friendship Hospital, Beijing 100029, China

received: February 26, 2019 ; accepted: May 12, 2019 ; published: May 29, 2019 ;

https://doi.org/10.18632/aging.101975
How to Cite

Copyright: Niu et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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 (psim=0.041, 0.043 and 0.030, respectively), and total cholesterol was a significant mediator for asthma (psim=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.

Abbreviations

RAGE: receptor for advanced glycation end products; COPD: chronic obstructive pulmonary disease; FEV1: forced expiratory volume in 1 second; FVC: forced vital capacity; CI: confidence interval; OR: odds ratio; BUN: blood urea nitrogen; HDLC: high-density lipoprotein cholesterol; LDLC: low-density lipoprotein cholesterol; TC: total cholesterol; TG: triglycerides; BMI: body mass index; FPG: fasting plasma glucose; HCY: homocysteine.