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Abstract
Background Urate is a strong antioxidant in plasma and may protect against lung function impairment. We tested the hypothesis that high plasma urate is causally associated with better lung function and low risk of respiratory symptoms and COPD.
Methods We measured lung function and plasma urate in 114 979 individuals from the Copenhagen City Heart Study and the Copenhagen General Population Study and genotyped for SLC2A9 rs7442295 and ABCG2 rs2231142 variants, previously associated with high plasma urate, in 110 152 individuals.
Results In the two studies combined, multivariable-adjusted 100 µmol/L higher plasma urate was associated with −1.54% (95% CI −1.67 to −1.40) lower FEV1 % predicted and −1.57% (95% CI −1.69 to −1.44) lower FVC % predicted observationally; the corresponding estimates for genetically determined 100 µmol/L higher plasma urate were −0.46% (95% CI −1.17 to 0.25) and −0.40% (95% CI −1.03 to 0.23). High plasma urate was also associated with higher risk of respiratory symptoms; however, genetically determined high plasma urate was not associated with respiratory symptoms. Finally, we identified 14 151 individuals with COPD and found ORs of 1.08 (95% CI 1.06 to 1.11) for COPD observationally and 1.01 (95% CI 0.88 to 1.15) genetically per 100 µmol/L higher plasma urate.
Conclusion High plasma urate was associated with worse lung function and higher risk of respiratory symptoms and COPD in observational analyses; however, genetically high plasma urate was not associated with any of these outcomes. Thus, our data do not support a direct causal relationship.
- urate
- lung function
- chronic obstructive pulmonary disease
- Mendelian randomisation
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Footnotes
Contributors CJK, SVK, SA, SFN and BGN designed the research. CJK analysed the data. CJK, SVK, SA, SFN and BGN interpreted the data and wrote the manuscript. BGN had the primary responsibility for final content. All authors had full access to all the data including statistical reports and tables, have read and approved the final manuscript, and take responsibility for the integrity and accuracy of the data analysis.
Funding This work was supported by the Michaelsen Foundation, Copenhagen, Denmark, the Danish Council for Independent Research, Medical Sciences, Copenhagen, Denmark, and Chief Physician Johan Boserup and Lise Boserup Foundation, Haslev, Denmark.
Disclaimer The funders had no role in design, collection, analysis or interpretation of data, or in the decision to submit for publication.
Competing interests None declared.
Ethics approval The studies were approved by Herlev and Gentofte Hospital and Danish Ethical Committees.
Provenance and peer review Not commissioned; externally peer reviewed.