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Updated: Jun 25, 2026

Cigarette Smoke Exposure in Mice using a Whole-Body Inhalation System
Published on: October 22, 2020
Smoke exposure interacts with ADAM33 polymorphisms in the development of lung function and hyperresponsiveness
N E Reijmerink1, M Kerkhof, G H Koppelman
1Department of Pulmonology, University medical Center Groningen, University of Groningen, Groningen, The Netherlands.
ADAM33 gene variants are linked to childhood asthma and bronchial hyperresponsiveness. In utero cigarette smoke exposure interacts with ADAM33, impacting lung function and asthma development.
Area of Science:
- Genetics and Respiratory Medicine
- Gene-Environment Interactions
- Pediatric Asthma Research
Background:
- ADAM33 is a key gene implicated in asthma development, particularly when combined with bronchial hyperresponsiveness (BHR).
- ADAM33 influences early-life lung function, including forced expiratory volume in 1 second (FEV1) decline.
- In utero and postnatal cigarette smoke exposure (CSE) negatively affect lung function and asthma development, potentially through interaction with ADAM33.
Purpose of the Study:
- To validate the association of ADAM33 with childhood lung function, BHR, and asthma.
- To investigate gene-environment interactions between ADAM33 and in utero/postnatal CSE in the PIAMA cohort.
Main Methods:
- Genotyping of six ADAM33 single-nucleotide polymorphisms (SNPs).
- Measurement of respiratory impedance (Rint) at ages 4 and 8.
- Assessment of FEV1, BHR, and asthma status at age 8.
Main Results:
- Specific ADAM33 alleles (rs511898 A, rs528557 C, rs2280090 A) were associated with increased asthma risk and BHR.
- Significant interaction was found between in utero CSE and ADAM33 SNPs (rs528557, rs3918396) for BHR development.
- In utero CSE interaction with rs3918396 affected Rint at age 8, and with rs528557 affected FEV1% predicted.
Conclusions:
- Replicated the association between ADAM33 and childhood asthma with BHR.
- Provided the first evidence that in utero CSE interacting with ADAM33 contributes to reduced lung function and BHR development.
- Highlighted the need for further research to confirm these gene-environment interaction findings.
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