Plasma urate, lung function and chronic obstructive pulmonary disease: A Mendelian randomisation study in 114 979 individuals from the general population

TY - JOUR

T1 - Plasma urate, lung function and chronic obstructive pulmonary disease

T2 - A Mendelian randomisation study in 114 979 individuals from the general population

AU - Kobylecki, Camilla J.

AU - Vedel-Krogh, Signe

AU - Afzal, Shoaib

AU - Nielsen, Sune F.

AU - Nordestgaard, Børge G.

PY - 2018

Y1 - 2018

N2 - 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 FEV 1 % 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.

AB - 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 FEV 1 % 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.

KW - chronic obstructive pulmonary disease

KW - lung function

KW - Mendelian randomisation

KW - urate

U2 - 10.1136/thoraxjnl-2017-210273

DO - 10.1136/thoraxjnl-2017-210273

M3 - Journal article

C2 - 29187594

AN - SCOPUS:85048045318

SN - 0040-6376

VL - 73

SP - 748

EP - 757

JO - Thorax

JF - Thorax

IS - 8

ER -