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Updated: Apr 30, 2026
09:50
Impact Assessment of Repeated Exposure of Organotypic 3D Bronchial and Nasal Tissue Culture Models to Whole Cigarette Smoke
Published on: February 12, 2015
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Nicotine Metabolism and Chronic Obstructive Pulmonary Disease: Mendelian Randomization and Phenotypic
Ting-Fen Ji1,2,3,4,5,6,7, Shi-Wen Song2,3,4,5,6,7, Ying Xie2,3,4,5,6,7,8
1Department of Tobacco Control and Prevention of Respiratory Diseases, China-Japan Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.
Summary
Genetically determined nicotine metabolism, measured by the nicotine metabolite ratio (NMR), is causally linked to chronic obstructive pulmonary disease (COPD) risk. This suggests NMR may aid in COPD risk stratification beyond smoking exposure.
Area of Science:
- Pulmonary Medicine
- Genetics
- Pharmacogenomics
Background:
- Smokers exhibit varied chronic obstructive pulmonary disease (COPD) risks despite similar smoking exposure.
- The independent role of genetically determined nicotine metabolism, quantified by the nicotine metabolite ratio (NMR), in COPD development is not fully understood.
Purpose of the Study:
- To investigate the causal relationship between nicotine metabolism (NMR) and COPD risk.
- To assess whether NMR influences COPD susceptibility independently of smoking exposure.
Main Methods:
- Two-sample Mendelian randomization (MR) analyses using genome-wide association study data to determine the causal effect of NMR on COPD.
- Colocalization analyses to identify shared genetic variants.
- Phenotypic analyses in a large cohort to compare COPD prevalence across different NMR phenotypes under controlled smoking exposure.
- Mediation analyses to evaluate the role of smoking behavior.
Main Results:
- MR analysis revealed a causal association between higher NMR and increased COPD risk (OR = 1.06).
- Shared causal variants were identified through colocalization.
- COPD prevalence was higher in normal metabolizers compared to slow metabolizers, even within similar smoking exposure levels.
- Smoking behavior partially mediated the association between NMR and COPD, accounting for 14.5% of the total effect.
Conclusions:
- Nicotine metabolism, indicated by NMR, is causally associated with COPD susceptibility.
- NMR may be a valuable biomarker for refining COPD risk assessment in smokers.
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