Asthma and lower airway diseaseCat exposure in early life decreases asthma risk from the 17q21 high-risk variant
Graphical abstract
Section snippets
Governance
We are aware of and comply with recognized codes of good research practice, including the Danish Code of Conduct for Research Integrity. We comply with national and international rules on the safety and rights of patients and healthy subjects, including Good Clinical Practice as defined in the European Union's Directive on Good Clinical Practice, the International Conference on Harmonisation's good clinical practice guidelines, and the Helsinki Declaration. We follow national and international
Results
Information on cat and dog ownership and rs7216389 SNP genotype was available in 92% (377/411) of the children from COPSAC2000. The genotype distribution was as follows: CC, 23% (86 children); CT, 48% (182 children); and TT, 29% (109 children). The clinical follow-up rate among children with the rs7216389 SNP genotype was 86% (325 children) at 12 years of age. Among these children, asthma was diagnosed in 26% (85 children) before age 12 years, and 13% (41 children) had current asthma at age
Principal findings
We found a gene-environment interaction between the rs7216389 genotype and cat and/or dog exposure from birth, attenuating the risk of asthma development during the first 12 years of life in children with the high-risk TT genotype but without any effect in children with the CC/CT genotype. This association seemed driven mainly by cat exposure. Similar observations were found for cat exposure and number of episodes with pneumonia and bronchiolitis from age 0 to 3 years. These findings might
References (32)
- et al.
Systematic review: exposure to pets and risk of asthma and asthma-like symptoms
J Allergy Clin Immunol
(2001) - et al.
Early exposure to house-dust mite and cat allergens and development of childhood asthma: a cohort study
Lancet
(2000) The Copenhagen Prospective Study on Asthma in Childhood (COPSAC): design, rationale, and baseline data from a longitudinal birth cohort study
Ann Allergy Asthma Immunol
(2004)- et al.
Neonatal bronchial hyperresponsiveness precedes acute severe viral bronchiolitis in infants
J Allergy Clin Immunol
(2012) - et al.
17q12-21 variants interact with smoke exposure as a risk factor for pediatric asthma but are equally associated with early-onset versus late-onset asthma in North Americans of European ancestry
J Allergy Clin Immunol
(2009) Early-life environmental determinants of allergic diseases and the wider pandemic of inflammatory noncommunicable diseases
J Allergy Clin Immunol
(2013)- et al.
The asthma epidemic
N Engl J Med
(2006) - et al.
Variations in pediatric asthma hospitalization rates and costs between and within Nordic countries
Chest
(2004) - et al.
Childhood asthma after bacterial colonization of the airway in neonates
N Engl J Med
(2007) - et al.
Effects of pet exposure in the first year of life on respiratory and allergic symptoms in 7-yr-old children. The SIDRIA-2 study
Pediatr Allergy Immunol
(2010)
Exposure to pets and atopy-related diseases in the first 4 years of life
Allergy
Does pet ownership in infancy lead to asthma or allergy at school age? Pooled analysis of individual participant data from 11 European birth cohorts
PLoS One
Gene-environment interaction in the onset of eczema in infancy: filaggrin loss-of-function mutations enhanced by neonatal cat exposure
PLoS Med
Intermittent inhaled corticosteroids in infants with episodic wheezing
N Engl J Med
Increased risk of pneumonia and bronchiolitis after bacterial colonization of the airways as neonates
Am J Respir Crit Care Med
Current asthma and respiratory symptoms among pupils in relation to dietary factors and allergens in the school environment
Indoor Air
Cited by (32)
Epigenome-wide association studies of allergic disease and the environment
2023, Journal of Allergy and Clinical ImmunologyDog ownership in infancy is protective for persistent wheeze in 17q21 asthma-risk carriers
2023, Journal of Allergy and Clinical ImmunologyGenetic and epigenetic links to asthma
2023, Asthma in the 21st Century: New Research AdvancesPrevention of Asthma: Targets for Intervention
2020, ChestCitation Excerpt :Multiple other studies have been equivocal or have shown an increase in atopy through allergen avoidance (Table 1).13-15,17-19 Recent studies confirm that the relationship between allergen exposure and asthma development is complicated, mediated by genes and gene methylation.20 Gene-environment interactions, such as the effects of pet exposure on those with different genotypes, have been studied.
Expression quantitative trait locus fine mapping of the 17q12–21 asthma locus in African American children: a genetic association and gene expression study
2020, The Lancet Respiratory MedicineCitation Excerpt :The overall high penetrance of the risk genotypes in both groups might be a result of inclusion of four high-risk CREW cohorts (accounting for 734 [46%] of 1613 European American children and 446 [51%] of 870 African American children of our CREW consortium; table 1), in which participants were selected on the basis of a family history of asthma or allergies (table 1). Furthermore, the less than 100% penetrance of asthma among both European American and African American children with the high-risk genotype (appendix p 16), and the central role of GSDMB in the innate immune response to intracellular microbes, is consistent with the many interaction effects on childhood-onset asthma risk between 17q12–21 genotypes and early life exposures, including tobacco smoke,18,31 rhinovirus and wheezing illnesses,19,20 farm animals,20 and pets.32 The present study had several strengths and limitations.
COPSAC is funded by private and public research funds all listed on www.copsac.com. The Lundbeck Foundation (grant no, R16-A1694), Danish Ministry of Health (grant no. 903516), Danish Council for Strategic Research (grant no. 0603-00280B), and Capital Region Research Foundation have provided core support for COPSAC.
Disclosure of potential conflict of interest: H. Bisgaard received consultancy fees from Chiesi Pharmaceuticals and Boehringer Ingelheim, and his institution received grants from the Lundbeck Foundation, Novo Nordisk Foundation, Danish Ministry of Health, and Danish Strategic Research Foundation for other works. The rest of the authors declare that they have no relevant conflicts of interest.