Genetic impact of CDHR3 on the adult onset of asthma and COPD

Clin Exp Allergy. 2020 Nov;50(11):1223-1229. doi: 10.1111/cea.13699. Epub 2020 Jul 23.


Background: Adult-onset asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases caused by complex gene-environment interactions. A functional single nucleotide polymorphism of cadherin-related family member 3 (CDHR3), known as a receptor of rhinovirus-C, is associated with childhood-onset asthma especially in atopic individuals.

Objective: Here, we identified risk factors for adult-onset asthma and COPD, focusing on the impact of the CDHR3 variant in atopic individuals.

Methods: We conducted a longitudinal, retrospective, observational cohort study of 1523 healthy adults with baseline examinations at Tsukuba Medical Center Hospital in 2008 and retrospectively identified new-onset, physician-diagnosed asthma or COPD from 2009 to 2018. We assessed risk factors by the Cox regression analysis. The impact of CDHR3 variant rs6967330 was also examined in individuals with pre-existing atopy.

Results: Over 10 study years, 103 people developed airway diseases (79 asthma and 24 COPD; 52 females, average onset-age 55 years old, range 38-80). Higher body mass index (BMI) and lower forced expiratory volume in one second/forced vital capacity (FEV1 /FVC) ratio were significant risk factors (BMI: HR 1.072 [95% CI 1.005-1.14], P = .034; FEV1 /FVC ratio: HR 1.091 [1.044-1.14], P = .00011). Restriction to atopic individuals saw the A allele at rs6967330 and lower FEV1 /FVC ratio to associate with adult-onset disease (A allele: HR 2.89 [1.57-5.20], P = .00062; FEV1 /FVC ratio: HR 1.10 [1.04-1.17], P = .0010).

Conclusion and clinical relevance: Genetic susceptibility to rhinovirus-C infection in atopic individuals is a risk factor for chronic airway diseases even in later life.

Keywords: adult-onset asthma; atopy; cadherin-related family member 3 (CDHR3); chronic obstructive pulmonary disease (COPD); genetics; rhinovirus.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Asthma / diagnosis
  • Asthma / epidemiology
  • Asthma / genetics*
  • Cadherin Related Proteins
  • Cadherins / genetics*
  • Enterovirus / pathogenicity*
  • Enterovirus Infections / diagnosis
  • Enterovirus Infections / epidemiology
  • Enterovirus Infections / genetics*
  • Enterovirus Infections / virology
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Japan / epidemiology
  • Longitudinal Studies
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / epidemiology
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors


  • CDHR3 protein, human
  • Cadherin Related Proteins
  • Cadherins
  • Membrane Proteins

Supplementary concepts

  • Rhinovirus C